status as of 06-jan-2017 status explanation of status pmr ... · pmr 2149-1 a 12-week, randomized,...

TRADE NAME (generic name) ORIGINAL DUE DATE

STATUS EXPLANATION OF STATUS PMR DESCRIPTION

ASMANEX HFA (mometasone furoate)

30-Sep-2015 Fulfilled

PMR 2149-1 A 12-week, randomized, placebo-controlled, dose-ranging efficacy and safety study of mometasone furoate metered dose inhaler (MDI) in the treatment of children ages 5-11 years with persistent asthma. Final Report Submission


28-Feb-2019 Released

FDA acknowledged on 07-Jan-2015 release PMR 2149-2 replacement with PMR 2149-4.

PMR 2149-2 A 12-week, double-blind, active-controlled, efficacy and safety study of two doses of mometasone furoate/formoterol fumarate combination MDI compared with the corresponding doses of mometasone furoate monotherapy MDI in the treatment of children ages 5-11 with persistent asthma. Final Report Submission


28-Feb-2019 Released

FDA acknowledged on 07-Jan-2015 release from PMR 2149-3 and replacement with PMR 2149-4

PMR 2149-3 A 6-month safety study, with a 6-month extension of two doses of mometasone furoate/formoterol fumarate combination MDI compared to fluticasone/salmeterol combination DPI in children 5-11 years of age with persistent asthma. Final Report Submission


28-Feb-2019 Ongoing

PMR 2149-4 Conduct a study to evaluate the efficacy and long-term safety of mometasone furoate/formoterol fumarate combination MDI (Dulera) and mometasone furoate MDI (Asmanex HFA) in children 5 to 11 years of age. Final Report Submission

BRIDION (sugammadex sodium)

30-Sep-2021 Pending

PMR 3003-1 A randomized, controlled trial evaluating the efficacy, safety, and pharmacokinetics of sugammadex injection when used to reverse neuromuscular blockade induced by either rocuronium or vecuronium must be conducted in pediatric patients ages birth to 17 years old. Final Report Submission

US Postmarketing Requirements Status as of 06-Jan-2017

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31-May-2017 Ongoing

PMR 3003-2 Conduct a postmarketing study to analyze the demographic characteristics, concomitant medication use, and comorbid conditions in patients who did not respond to sugammadex reversal in the development program, in postmarket studies that have been conducted, or as described in cases of non-response/lack of efficacy reported as postmarketing adverse events. The goal of the study is to determine the characteristics and profile of patients who would be expected to be non-responders. The study should also assess the occurrence of hypersensitivity or anaphylaxis, prolonged ventilator support and sedation, and anoxia in these patients. Final Report Submission


31-Aug-2020 Pending

PMR 3003-3 Conduct a postmarketing clinical trial comparing sugammadex to placebo and/or drugs approved for the management of the reversal of the effects of neuromuscular blockade induced by rocuronium or vecuronium in a population of American Society of Anesthesiologists Class 3 and 4 patients. The goal of the trial is characterization of the risks of bradycardia and other cardiac arrhythmias after sugammadex administration in this population that may have more severe outcomes related to cardiac arrhythmias experienced during reversal of neuromuscular blockade. Prespecify the case definition of bradycardia, tachycardia, and the other cardiac arrhythmias of interest. Final Report Submission

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31-Mar-2019 Pending

PMR 3003-4 Conduct a postmarketing clinical trial comparing sugammadex to placebo and/or drugs approved for the management of the reversal of the effects of neuromuscular blockade induced by rocuronium or vecuronium in patients with morbid obesity. The goal of the trial is to evaluate the safety of sugammadex (including the serious adverse outcomes of anaphylaxis or hypersensitivity) and to generate data to support dosing recommendations in morbidly obese patients, specifically whether to dose by actual vs. ideal body weight. Prespecify the case definition of morbid obesity that will establish who will be included in the trial. Final Report Submission

CANCIDAS (caspofungin acetate)

31-Jul-2020 Ongoing

PMR 1 Deferred pediatric study under PREA for the treatment of candidemia and Candida infections in pediatric patients ages 0 to 3 months. Final Report Submission

CUBICIN (daptomycin)

31-Aug-2015 Submitted

Final Clinical Study Report submitted on June 2, 2015. FDA notified company that labeling supplement must also be submitted to fulfill PMR. Pediatric labeling sNDA was submitted on June 30, 2016

PMR 2864-1 Conduct a multicenter, evaluator blinded, randomized comparator study to assess the safety, efficacy and PK of three age dependent doses of IV daptomycin administered for up to 14 days in pediatric patients aged 1 to 17 years, inclusive with cSSSI caused by Gram-positive pathogens.


18-Jun-2008 Released

Per FDA letter dated 11Feb2015, sponsor released from PMR 47-2. Replacement PMR 2864-1 issued in same letter.

PMR 47-2 Deferred pediatric study under PREA for the treatment of complicated skin and skin structure infections (cSSSI) in pediatric patients ages 3 months to less than 18 years.


31-Dec-2011 Released

FDA Acknowledged on 19-Nov-2015 release from PMR 804-1 and replace with PMR 804-7.

PMR 804-1 Deferred pediatric study under PREA for the treatment of Staphylococcus aureus bloodstream infections (bacteremia), including those with right-sided infective endocarditis, caused by methicillin-susceptible and methicillin-resistant isolates. Final Report Submission.

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15-Mar-2017 Ongoing

PMR 804-7 Conduct a multicenter, evaluator-blinded, randomized comparator study designed to evaluate the safety, efficacy, pharmacokinetics of IV daptomycin administered for up to 14 days in the treatment of pediatric patients age 1 to 17 years with S. aureus bacteremia versus standard of care. Final Report Submission.

DIFICID® (fidaxomicin)

30-Apr-2013 Fulfilled

PMR 1757-001 Conduct a prospective clinical trial of 10 days of Dificid (fidaxomicin) in at least 32 pediatric patients (6 months to less than 18 years of age) with C. difficile-associated diarrhea to evaluate the safety and pharmacokinetics (including serum and fecal concentrations) of Dificid (fidaxomicin). Final Report Submission


31-Jul-2017 Ongoing

PMR 1757-002 Conduct a prospective, randomized clinical trial to demonstrate safety and effectiveness of Dificid (fidaxomicin) compared to vancomycin in pediatric patients (6 months to less than 18 years of age) with C. difficile-associated diarrhea. Final Report Submission


31-Mar-2017 Ongoing

PMR 1757-003 Conduct a prospective study over a five-year period after introduction of Dificid (fidaxomicin) to the market to determine if decreased susceptibility to Dificid (fidaxomicin) is occurring in C. difficile. Provide a detailed protocol describing the study to the Agency for review and comment before commencing the study. Final Report Submission

DULERA (mometasone furoate (+) formoterol fumarate)

31-Jul-2012 Fulfilled

PMR 1658-1 Deferred pediatric trial under PREA to compare the pharmacodynamics of DULERA with and without a spacer in children 5 to 11 years of age. Final Report Submission

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30-Nov-2014 Released

PMR 1658-2 Deferred pediatric trial under PREA to compare the pharmacokinetics of DULERA with and without a spacer in children 5 to 11 years of age. Final Report Submission


31-Mar-2014 Released

PMR 1658-3 Deferred pediatric trial under PREA to evaluate the effects of DULERA on the HPA axis in children 5 to 11 years of age. In lieu of an HPA axis study, you may provide robust data to demonstrate that the systemic exposure of mometasone from DULERA is comparable or lower than that from the mometasone dry powder inhaler. Final Report Submission


31-Aug-2014 Fulfilled

PMR 1658-4 Deferred pediatric trial under PREA to evaluate the safety and efficacy of multiple doses of mometasone MDI in children 5 to 11 years of age with asthma. Final Report Submission


31-Jan-2017 Released

FDA acknowledged on 07-Jan-2015 release from PMR 1658-5 and replacement with PMR 1658-7.

PMR 1658-5 Deferred pediatric trial under PREA to evaluate the safety and efficacy of DULERA compared to mometasone MDI in children 5 to 11 years of age with asthma. This study will be 12- 26 weeks duration. Final Report Submission



FDA acknowledged on 07-Jan-2015 release from PMR 1658-6 and replacement with PMR 1658-7.

PMR 1658-6 Deferred pediatric trial under PREA to evaluate the long-term safety of DULERA in children 5 to 11 years of age with asthma. This study will be 26 weeks duration with a 6 month extension. Final Report Submission

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28-Feb-2019 Ongoing

PMR 1658-7 Conduct a study to evaluate the efficacy and long-term safety of mometasone furoate/formoterol fumarate combination MDI (Dulera) and mometasone furoate MDI (Asmanex HFA) in children 5 to 11 years of age. Final Report Submission


30-Jun-2017 Ongoing

PMR 1751-1 A randomized, double-blind, 26-week, active-controlled clinical trial comparing Dulera (mometasone furoate and formoterol fumarate) Inhalation Aerosol and mometasone furoate to evaluate the risk of serious asthma outcomes (hospitalizations, intubation, death) in 11,700 adult and adolescent patients 12 years of age and older with persistent asthma. Final Report Submission

EMEND (aprepitant)

31-Oct-2013 Fulfilled

PMR 1395-7 Deferred pediatric studies in patients 2 years to 17 years of age for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy, including high-dose cisplatin. Final Report Submission

EMEND (aprepitant)

31-Oct-2013 Fulfilled

PMR 331-1 Deferred pediatric study under PREA for the use of Emend (aprepitant) in the prevention of nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy in pediatric patients 6 months to less than 17 years of age. Final Report Submission

EMEND (aprepitant)

31-Dec-2009 Ongoing

FDA INFO: Original Final Report due date: 12/31/09. Deferral extension granted per FDA letter dated 4/12/13. The final report milestone date extended until 1/31/20.

PMR 574-1 Deferred pediatric study under PREA for the treatment of post-operative nausea and vomiting pediatric patients ages 0 to less than 17 years of age. Final Report Submission

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EMEND for Injection (fosaprepitant dimeglumine)


PMR 1450-1 A study in adolescents and younger pediatric patients receiving emetogenic chemotherapy (HEC or MEC) to evaluate fosaprepitant PK, safety, and tolerability. Final Report Submission


31-May-2014 Released

PMR 1663-1 A PK/PD study to characterize aprepitant PK parameters following administration of a single dose of intravenous fosaprepitant, in combination with a 5HT3 antagonist and dexamethasone, in pediatric cancer patients ages 0 to 17 years undergoing treatment with highly or moderately emetogenic chemotherapy. You must conduct this study with an age appropriate formulation. Final Report Submission



PMR 1663-2 An adequate, placebo-controlled, double-blind, randomized, add-on design, superiority study to evaluate the safety and efficacy of a single dose of intravenous fosaprepitant, in combination with a 5HT3 antagonist, as compared to standard therapy (a 5HT3 antagonist) in pediatric cancer patients ages 0 to 17 years undergoing treatment with highly or moderately emetogenic chemotherapy. You must conduct this study with an age appropriate formulation. Final Report Submission

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31-Dec-2017 Ongoing

PMR 1663-3 A PK/PD study to characterize aprepitant PK parameters following administration of a single dose of intravenous fosaprepitant, in combination with a 5HT3 antagonist and dexamethasone, in pediatric cancer patients ages 0 to 17 years undergoing treatment with highly emetogenic chemotherapy. You must conduct this study with an age appropriate formulation. Use modeling and simulation including the results of the above study to identify 1-Day and 3-Day intravenous fosaprepitant doses in pediatric patients 0 to 17 years of age that provide similar aprepitant PK exposures to pediatric aprepitant doses and exposures which have demonstrated acceptable safety and efficacy profiles in patients receiving single and multi-day chemotherapy regimens, respectively. Final Report Submission

ENTEREG® (alvimopan)


The FDA has released this PMR and will be replaced, due to approval of a new pediatric study, with the new required study PMR# 918-4.

PMR 1- Conduct a study of Entereg for the acceleration of gastrointestinal recovery in pediatric patients age greater than 1 month up to 16 years undergoing bowel resection surgery. The study will measure the time to first tolerated feed, population PK parameters, the proportion of postoperative days with stool passed while in hospital, length of hospital stay, the need for postoperative nasogastric tube insertion for symptoms of POI, and safety. Final Report Submission



The FDA released Merck from this PMR 918-2 due to their approval of Merck's new pediatric study, 0mo to 10yrs, new PMR number is 918-5.

PMR 2- Conduct a study of Entereg for the acceleration of gastrointestinal recovery in pediatric patients age 0 to 1 month undergoing bowel resection surgery. The study will measure population PK parameters, safety, and the time to first tolerated feed while in the hospital. Final Report Submission

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30-Dec-2022 Pending

PMR 918-4, Conduct a study of Entereg (alvimopan) for the acceleration of gastrointestinal recovery in pediatric patients aged 10 to 18 years undergoing partial bowel resection surgery with primary anastomosis. The study will measure the time to first tolerated feed and time to first bowel movement while in the hospital, population pharmacokinetic parameters, length of hospital stay, the need for postoperative nasogastric tube insertion for symptoms of postoperative ileus, and safety. Final Protocol Submission: July 2016. Study Start: December 2016, Final Report Submission: December 2022. Under PREA (21 U.S.C. 355c), all applications for new active ingredients, new indications, new dosage forms, new dosing regimens, or new routes of administration are required to contain an assessment of the safety and effectiveness of the product for the claimed indication(s) in pediatric patients unless this requirement is waived, deferred, or inapplicable. Your new pediatric studies, which replace PMRs 918-1 and 918-2, are required postmarketing studies. The status of these postmarketing studies must be reported annually according to 21 CFR 314.81 and section 505B(a)(3)(C) of the FDCA.

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30-Jun-2028 Pending

PMR 918-5, Conduct a study of Entereg (alvimopan) for the acceleration of gastrointestinal recovery in pediatric patients aged 0 months to 10 years undergoing partial bowel resection surgery with primary anastomosis. The study will measure population pharmacokinetic parameters, safety, and time to first bowel movement and tolerated feed while in the hospital. Final Protocol Submission: September 2022, Study Start: May 2023, Final Report Submission: June 2028. Under PREA (21 U.S.C. 355c), all applications for new active ingredients, new indications, new dosage forms, new dosing regimens, or new routes of administration are required to contain an assessment of the safety and effectiveness of the product for the claimed indication(s) in pediatric patients unless this requirement is waived, deferred, or inapplicable. Your new pediatric studies, which replace PMRs 918-1 and 918-2, are required postmarketing studies. The status of these postmarketing studies must be reported annually according to 21CFR 314.81 and section 505B(a)(3)(C) of the FDCA.


30-Jun-2012 Fulfilled

PMR Clinical Trial #1 A multi-center, double-blind, placebo-controlled, parallel group clinical trail of entereg for the mangement or postoperative ileus in patients undergoing radical cystectomy. Final Report Submission.

ISENTRESS (raltegravir potassium)


PMR 1880-1 Conduct a clinical trial to evaluate the effect of co-administration and staggered administration of calcium- or magnesium/aluminum-containing antacids on the pharmacokinetics of raltegravir in HIV-infected subjects on a stable raltegravir-containing regimen. Final Report Submission

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31-Jan-2015 Ongoing

Deferral extension approved 31-Oct-2014. New milestone due date: 31-Dec-2016. Additional deferral extension approved on 30-Jun-2016. New milestone due date: 30-Sep-2017

PMR 1881-1 Deferred pediatric study under PREA to evaluate the safety and pharmacokinetics of raltegravir in HIV-exposed neonates (born to HIV-infected mothers). This multiple-dose pharmacokinetic and safety study will evaluate raltegravir in addition to the standard of care in HIV-exposed neonates from ages 0 to 4-6 weeks. HIV-exposed neonates will have safety assessments, on or off treatment (as appropriate), for a minimum of 24 weeks after start of raltegravir therapy. Final Report Submission. This study is being conducted for NDA 22145, NDA 203045 and NDA 205786.



PMR 582-2 Deferred pediatric study under PREA for the treatment of HIV-1 infection in pediatric subjects from 2 to 18 years of age. This study will determine raltegravir exposure (pharmacokinetic profile) followed by 24 weeks of dosing. Efficacy will be based on viral load reduction through 24 weeks of dosing and safety will be monitored for a minimum of 24 weeks to support raltegravir dose selection, safety, and efficacy in this population. Final Report Submission



PMR 582-3 Deferred pediatric study under PREA for the treatment of HIV-1 infection in pediatric subjects from 4 weeks to 2 years of age. This study will determine raltegravir exposure (pharmacokinetic profile) followed by 24 weeks of dosing. Efficacy will be based on viral load reduction through 24 weeks of dosing and safety will be monitored for a minimum of 24 weeks to support raltegravir dose selection, safety, and efficacy in this population. Final Report Submission

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ISENTRESS Chewable Tablets (raltegravir potassium)

31-Jan-2015 Released

PMR 1846-1 Deferred pediatric study under PREA for the treatment of HIV-1 infection in pediatric subjects from ages 0 to <4 weeks of age. The study will determine the safety, antiviral activity and pharmacokinetic profile of raltegravir in neonates. The antiviral activity will be based on the results of virologic response over at least 24 weeks of dosing and safety will be monitored for a minimum of 24 weeks. Final Report Submission

ISENTRESS Chewable Tablets (raltegravir potassium)

31-Jan-2015 Ongoing



ISENTRESS® (raltegravir potassium) Granules for Suspension (raltegravir potassium)

31-Jan-2015 Ongoing



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JANUMET (sitagliptin phosphate (+) metformin hydrochloride) 15-Jun-2011 Fulfilled

PMR 1603 A 3-month pancreatic safety study in a diabetic rodent model treated with sitagliptin. Final Report Submission

JANUMET (sitagliptin phosphate (+) metformin hydrochloride)

30-Sep-2011 Ongoing

Deferral extension approved 25-Jan-2016. New due date for final report submission is 31-Jul-2019.

PMR 856-1, Deferred pediatric study under PREA for the treatment of type 2 diabetes in pediatric patients ages 11 to 16, inclusive. Final Report Submission

JANUMET XR (sitagliptin phosphate (+) metformin hydrochloride) 01-Jun-2014 Fulfilled

PMR 1802-1 A pharmacokinetic study of JANUMET XR in pediatric patients 10 through17 years of age (inclusive) with type 2 diabetes mellitus. Final Report Submission

JANUMET XR (sitagliptin phosphate (+) metformin hydrochloride)


PMR 1802-2 A 54-week, randomized, double-blind placebo-controlled trial to evaluate the efficacy and safety of JANUMET XR vs. metformin in pediatric patients who are inadequately controlled on diet and exercise. You must also evaluate whether pediatric patients can safely swallow JANUMET XR over the course of the trial. Final Report Submission



PMR 1802-3 A 54-week, randomized, double-blind placebo-controlled trial to evaluate the efficacy and safety of JANUMET XR versus metformin extented-release in pediatric patients who are inadequately controlled on metformin immediate release. You must also evaluate whether pediatric patients can safely swallow JANUMET XR over the course of the trial. Final Report Submission

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31-Jul-2019 Ongoing

PMR 1802-4: A 54-week, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of JANUMET XR versus metformin extended-release in pediatric patients who are inadequately controlled on metformin immediate release The timetable stated in the January 25,2016, deferral extension granted letter for PMR 1802-3 will remain unchanged and apply to PMR 1802-4: Final Report Submission: July 31, 2019

JANUVIA (sitagliptin phosphate)


PMR 1602 A 3-month pancreatic safety study in a diabetic rodent model treated with sitagliptin. Final Report Submission

JANUVIA (sitagliptin phosphate)

31-Dec-2010 Ongoing

Deferral extension approved 25-Jan-2016. New due date for final report submission is 31-Jul-2019.

PMR 224-1, Deferred pediatric study under PREA for the treatment of type 2 diabetes in pediatric patients ages 11 to 16, inclusive. Final Report Submission

JUVISYNC (sitagliptin phosphate (+) simvastatin)

31-Jul-2015 Released

Withdrawal of the JUVISYNC (MK-0431D, NDA 202,343) NDA was posted in Federal Register December 5, 2014.

PMR 1826-1 A randomized, double-blind, active-controlled clinical trial to study the effect of sitagliptin and simvastatin fixed-dose combination versus sitagliptin on glycemic control in type 2 diabetic patients on background metformin therapy. Final Report Submission

KEYTRUDA (pembrolizumab)

31-Jan-2017 Fulfilled

PMR 2770-1 - Conduct and submit the results of a multicenter, randomized trial or trials establishing the superiority of pembrolizumab over standard therapy in adult patients with unresectable or metastatic melanoma who are refractory to ipilimumab or who have not been previously treated with ipilimumab - Final Report Submission

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30-Sep-2016 Submitted

PMR 2952-1 Conduct and submit the results of a multicenter, randomized clinical trial establishing the superiority of Keytruda over available therapy in patients with metastatic, PDL1-positive NSCLC who have been previously treated with platinum-containing chemotherapy. Final Report Submission


30-Apr-2018 Ongoing

PMR 3100-1: Conduct and submit the results of at least one multicenter, randomized clinical trial establishing the superiority of pembrolizumab over available therapy as determined by an improvement in overall survival in patients with metastatic squamous cell carcinoma of the head and neck. Final Report Submission: April 2018

NOXAFIL (posaconazole)

30-Sep-2017 Ongoing

PMR 2090-1 Conduct a trial in patients, ages 2 to < 18 years, to evaluate the pharmacokinetic (PK), safety, and tolerability of two new formulations ofposaconazole (IV solution and/or new age- appropriate oral formulation) in immunocompromised pediatric patients with known or expected neutropenia. Final Report Submission. This study is the same one required for PMR 2132-1.


31-Mar-2021 Pending

PMR 2090-2: Conduct a comparative, double-blind, randomized, multi-center trial, in patients ages 2 to< 18 years, to evaluate the safety, efficacy, and tolerability of posaconazole for the prophylaxis of invasive fungal infections (IFI) in pediatric patients with known or expected neutropenia. Final Report Submission. This study is the same one required for PMR 2132-2

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30-Sep-2017 Ongoing

PMR 2132-1: Conduct a trial in patients, ages 2 to < 18 years, to evaluate the pharmacokinetic (PK), safety, and tolerability of two new formulations of posaconazole (IV solution and/or new age-appropriate oral formulation) in immunocompromised pediatric patients with known or expected neutropenia. Final Report Submission. This study is the same one required for PMR 2090-1.


31-Mar-2021 Pending

PMR 2132-2: Conduct a comparative, double-blind, randomized, multi-center trial, in patients ages 2 to < 18 years, to evaluate the safety, efficacy, and tolerability of posaconazole for the prophylaxis of invasive fungal infections (IFI) in pediatric patients with known or expected neutropenia. Final Report Submission. This study is the same one required for PMR 2090-2.


15-Sep-2011 Released

FDA acknowledged new target date of 12/31/18 for study report. FDA Released MAH from commitment on 17-OCT-2016

PMR 28-3 Deferred pediatric study under PREA for the prophylaxis of invasive Aspergillis and Candida infections in patients, who are at risk of developing these infections in pediatric patients two years to twelve years of age. Final Report Submission


20-Oct-2011 Released

FDA released MAH from commitment on 6/26/2015

PMR 864-1 Deferred pediatric study under PREA for the treatment of oropharyngeal candidiasis in pediatric patients ages zero to sixteen years of age. Final Report Submission

PEGINTRON (peginterferon alfa-2b)

31-Mar-2014 Fulfilled

PMR Completion of the 5-year follow-up observational study of subjects enrolled in Part 2 of the pediatric study P02538, to assess long-term or delayed toxicity including the effect of PegIntron on height and weight and the durability of treatment response. Submit data for at least 50 pediatric subjects completing the 5 year follow-up. Final Report Submission

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RAGWITEK (short ragweed pollen allergen extract)

30-Sep-2019 Ongoing

Deferred pediatric study, protocol #P008, under PREA to evaluate both safety and efficacy of RAGWITEK as immunotherapy for the treatment of short ragweed pollen-induced allergic rhinits, with or without conjunctivitis, confirmed by positive skin test or in vitro testing for pollen specific IgE antibodies for short ragweed pollen in pediatric subjects aged 5 to 17 years. Final Report Submission

RAGWITEK (short ragweed pollen allergen extract)

30-Sep-2019 Pending

Deferred pediatric study, protocol #P009, under PREA to evaluate the safety of RAGWITEK as immunotherapy for the treatment of short ragweed pollen-induced allergic rhinitis, with or without conjunctivitis, confirmed by positive skin test or in vitro testing for pollen specific IgE antibodies for short ragweed pollen in pediatric subjects aged 5 to 17 years. Final Report Submission

REMERON (mirtazapine)

31-Dec-2015 Fulfilled

PMR 2176-1 A single-center randomized, placebocontrolled and active-controlled thorough QT (TQT) trial of Remeron (mirtazapine) in normal (or healthy) subjects. Please refer to ICH E14 guidance to design the trial and submit the protocol to the agency for comments. The doses studied should ensure the clinical concentration- response relationship for QTc prolongation is characterized, including exploration of higher concentrations than those achieved following the anticipated therapeutic dose at the steady state. Include the highest tolerable dose in the trial. Final Report Submission.

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REMERON SOLTAB (mirtazapine)


PMR 2176-1 A single-center randomized, placebocontrolled and active-controlled thorough QT (TQT) trial of Remeron (mirtazapine) in normal (or healthy) subjects. Please refer to ICH E14 guidance to design the trial and submit the protocol to the agency for comments. The doses studied should ensure the clinical concentration- response relationship for QTc prolongation is characterized, including exploration of higher concentrations than those achieved following the anticipated therapeutic dose at the steady state. Include the highest tolerable dose in the trial. Final Report Submission

SAPHRIS (asenapine maleate)

01-Dec-2016 Other

The FDA commitments for this product have transferred to Forest Labs as of 31-Jan-2014

PMR 1496-1 A deferred pediatric study under PREA for the treatment of schizophrenia in pediatric patients ages 13 to 17 years. A study to obtain pharmacokinetic data and provide information pertinent to dosing of asenapine sublingual tablets in the relevant pediatric population. Final Report Submission


01-Dec-2016 Other


PMR 1496-2 A deferred pediatric study under PREA for the treatment of schizophrenia in pediatric patients ages 13 to 17 years. A study of the efficacy and safety of asenapine sublingual tablets in the relevant pediatric population. Final Report Submission


01-Dec-2016 Other


PMR 1496-3 A deferred pediatric study under PREA for the treatment of acute manic or mixed episodes associated with Bipolar I Disorder ages 10 to 17 years. A study to obtain pharmacokinetic data and provide information pertinent to dosing of asenapine sublingual tablets in the relevant pediatric population. Final Report Submission

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01-Dec-2016 Other


PMR 1496-4 A deferred pediatric study under PREA for the treatment of acute manic or mixed episodes associated with Bipolar I Disorder ages 10 to 17 years. A study of the efficacy and safety of asenapine sublingual tablets in the relevant pediatric population. Final Report Submission

SINGULAIR (montelukast sodium)


PMR Deferred pediatric study under PREA for the prevention of exercise-induced bronchoconstriction in pediatric patients ages 4 - 14 years of age. NDA 20-829. Final Report Submission







SIVEXTRO® (tedizolid phosphate)

30-Jun-2017 Ongoing

PMR 2159-1 Conduct a randomized Single-Blind, Multicenter Safety and Efficacy Study of Intravenous to Oral SIVEXTRO (tedizolid phosphate) and Intravenous to Oral Comparator for the Treatment of Acute Bacterial Skin and Skin Structure Infections in Pediatric Patients Aged 12 to <18 Years. Final Report Submission This study is being conducted for both NDA 205435 and NDA 205436.

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30-Jun-2017 Ongoing

PMR 2159-1 Conduct a randomized Single-Blind, Multicenter Safety and Efficacy Study of Intravenous to Oral SIVEXTRO (tedizolid phosphate) and Intravenous to Oral Comparator for the Treatment of Acute Bacterial Skin and Skin Structure Infections in Pediatric Patients Aged 12 to <18 Years. Final Report Submission This study is being conducted for both NDA 205435 and NDA 205436.


31-May-2019 Pending

PMR 2159-2 Conduct a randomized, Single-Blind, Multicenter Safety and Efficacy Study of Intravenous to Oral SIVEXTRO (tedizolid phosphate) and Intravenous to Oral Comparator for the Treatment of Acute Bacterial Skin and Skin Structure Infections in Pediatric Patients Aged >3 Months to < 12 years. Final Report Submission This study is being conducted for both NDA 205435 and NDA 205436.


31-May-2019 Pending

PMR 2159-2 Conduct a randomized, Single-Blind, Multicenter Safety and Efficacy Study of Intravenous to Oral SIVEXTRO (tedizolid phosphate) and Intravenous to Oral Comparator for the Treatment of Acute Bacterial Skin and Skin Structure Infections in Pediatric Patients Aged >3 Months to < 12 years. Final Report Submission This study is being conducted for both NDA 205435 and NDA 205436.


29-Feb-2020 Pending

PMR 2159-3: Conduct an open-Label, Multicenter Study of 10-14 days IV SIVEXTRO (tedizolid phosphate) for hospital-acquired late onset sepsis in full term and preterm neonates and infants aged 5 days to < 3months. Final Report Submission This study is being conducted for both NDA 205435 and NDA 205436.

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29-Feb-2020 Pending

PMR 2159-3: Conduct an open-Label, Multicenter Study of 10-14 days IV SIVEXTRO (tedizolid phosphate) for hospital-acquired late onset sepsis in full term and preterm neonates and infants aged 5 days to < 3months. Final Report SubmissionThis study is being conducted for both NDA 205435 and NDA 205436.


30-Apr-2017 Ongoing

PMR 2159-4: Conduct a Phase 1, Single-Dose Safety and Pharmacokinetic Study of Oral and IV SIVEXTRO in Inpatients 2 to <12 Years of Age. Final Report Submission This study is being conducted for both NDA 205435 and NDA 205436.


30-Apr-2017 Ongoing

PMR 2159-4: Conduct a Phase 1, Single-Dose Safety and Pharmacokinetic Study of Oral and IV SIVEXTRO in Inpatients 2 to <12 Years of Age. Final Report Submission This study is being conducted for both NDA 205435 and NDA 205436.


31-Jul-2019 Pending

PMR 2159-5 Conduct a Phase 1 Single-Dose Safety and Pharmacokinetic Study of Oral and Intravenous SIVEXTRO in Inpatients Under 2 Years Old. Final Report Submission. This study is being conducted for both NDA 205435 and NDA 205436.


31-Jul-2019 Pending

PMR 2159-5 Conduct a Phase 1 Single-Dose Safety and Pharmacokinetic Study of Oral and Intravenous SIVEXTRO in Inpatients Under 2 Years Old. Final Report Submission. This study is being conducted for both NDA 205435 and NDA 205436.

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31-Aug-2020 Ongoing

PMR 2159-6 Conduct US surveillance studies for five years from the date of marketing SIVEXTRO to determine if resistance to tedizolid has developed in those organisms specific to the indication in the label for ABSSSI. Final Report Submission. This study is being conducted for both NDA 205435 and NDA 205436.


31-Aug-2020 Ongoing

PMR 2159-6 Conduct US surveillance studies for five years from the date of marketing SIVEXTRO to determine if resistance to tedizolid has developed in those organisms specific to the indication in the label for ABSSSI. Final Report Submission. This study is being conducted for both NDA 205435 and NDA 205436.

SYLATRON (peginterferon alfa-2b)


PMR #1 To develop a validated, sensitive, and accurate assay for the detection of neutralizing antibodies to peginterferon alfa-2b, including procedures for accurate detection of neutralizing antibodies to peginterferon alfa-2b in the presence of peginterferon alfa-2b levels that are expected to be present in the serum or plasma at the time of patient sampling. In the event such an assay cannot be developed, evidence of due diligence in attempting to develop the assay will be provided. Final Report Submission

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15-Jul-2020 Released

PMR #2 To conduct a randomized, multicenter, observation-controlled trial of peginterferon alfa-2b as adjuvant therapy in 1200 patients with ulcerated primary cutaneous melanoma with negative sentinel lymph node biopsy (T1b-T4bN0M0) randomized 1:1 to peginterferon alfa-2b 3.0 mcg/kg SC administered weekly for 24 months or observation alone for 24 months. The trial will characterize toxicity of treatment, specifically debilitating fatigue, depression, and anorexia, and evaluate relapse-free survival (RFS). Secondary endpoints will include overall survival. The trial will be powered to detect an increase in RFS rate by 6.8% at 2 years, by 9.4% at 5 years, and by 10% at 10 years. The trial will be powered to detect a hazard ratio of 0.7 for overall survival. The trial design and statistical analysis plan must adequately address the comments provided to you in our December 10, 2010, letter to IND 7194 regarding proposed trial 18081. Final Report Submission


31-May-2014 Fulfilled

PMR #3 To conduct a clinical trial that will assess the effect of peginterferon alfa-2b on the QT/QTc interval. This QT assessment must be performed in an adequate number of subjects receiving the highest clinical dose approved and at the steady state maximum therapeutic exposure that is anticipated in patients with melanoma to ensure that changes of 20 ms in QTc interval can be excluded. ECG with time-matched PK samples will be collected at the anticipated steady state concentration and across the entire dosing interval at steady state. ECGs will be collected in replicates and centrally read. Statistical analyses will include central tendency analysis, concentration-QT analysis and categorical analysis. Final Report Submission

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PMR #4 To conduct an assessment of anti-drug antibody (ADA) and neutralizing ADA responses to peginterferon alfa-2b with validated assays capable of sensitively detecting ADA responses in the presence of peginterferon alfa-2b levels that are expected to be present at the time of patient sampling. ADA responses will be evaluated in all available samples from Trial EORTC 18991. Samples tested positive for binding ADA will be evaluated for neutralizing ADA responses. The final report will include information on the level of peginterferon alfa-2b in each patient's test sample at each sampling time point. Final Report Submission


31-May-2014 Fulfilled

PMR #5 To conduct a drug interaction trial in 24 healthy subjects receiving subcutaneous peginterferon alfa-2b 6 mcg/kg once weekly for four weeks with probe substrates for multiple cytochrome P450 enzymes administered before the first dose and after the last dose of peginterferon alfa-2b. Pharmacokinetic blood and urine samples will be collected after the administration of the probe substrates and peginterferon alfa-2b (up to 168 hours) to measure enzyme activities and peginterferon alfa-2b systemic exposure. Final Report Submission

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31-Aug-2013 Fulfilled

PMR #6 To conduct a dedicated clinical trial assessing the safety and pharmacokinetics (PK) of peginterferon alfa-2b in accordance with the FDA Guidance for Industry: Pharmacokinetics in Patients with Impaired Renal Function - Study Design, Data Analysis and Impact on Dosing and Labeling. The renal function subgroups should have similar demographic characteristics with respect to age, gender and weight. The number of patients enrolled in the trial should be sufficient to detect clinically important PK differences that would warrant dosage adjustment recommendation. The frequency and duration of blood sampling should be sufficient to accurately estimate relevant PK parameters for the parent drug. A data analysis plan should be included in the final protocol submitted to FDA. Final Report Submission

VICTRELIS (boceprevir)

31-May-2013 Released

PMR 1767-01 Conduct a single-dose pharmacokinetics study of boceprevir in treatment naïve pediatric subjects 3 through 17 years of age to determine weight-based dosing for children that will result in exposures similar to those observed in adults. Final Report Submission.



PMR 1767-10 Conduct an in vivo drug-drug interaction trial between boceprevir and a selective serotonin reuptake inhibitor (SSRI) (e.g. escitalopram). Final Report Submission

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31-Oct-2015 Released

PMR 1767-2 Conduct a trial to evaluate safety and treatment response of boceprevir in combination with pegylated interferon and ribavirin as measured by sustained virologic response (SVR) in pediatric subjects 3 through 17 years of age, including previously untreated subjects and those who have failed a prior course of pegylated interferon and ribavirin therapy. This trial should include at least 5 years follow-up of pediatric subjects to characterize long-term safety of boceprevir, including growth assessment and sexual maturation in pediatric subjects, to determine the durability of response and to characterize boceprevir resistance-associated substitutions. Final Report Submission

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PMR 1767-3 Conduct a study to assess the impact of boceprevir treatment-emergent NS3 amino acid substitutions (those that have been observed but not characterized phenotypically) on the anti-HCV activity of boceprevir in the HCV replicon system. Potentially novel resistance-associated substitutions should also be evaluated. The HCV replicon genotype/subtype background used should be consistent with the background in which the specific substitutions have been observed in treated patients. Evaluations should include HCV replicons with previously characterized resistance-associated substitutions spanning the range of susceptibilities as reference standards. Specific examples of substitutions to be assessed include the following: a. D168N, with and without linked R155T, genotype 1a replicon b. V107I, with and without linked V36M+R155K, genotype 1a replicon c. P146S, with and without linked V36M+R155K, genotype 1a replicon d. I170V, genotype 1a replicon e. V36M, R155K and V36M+R155K, genotype 1a replicon Final Report Submission

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PMR 1767-4 Conduct pooled analyses to characterize the impact of detectable baseline boceprevir resistance-associated polymorphisms on the efficacy of boceprevir + Peg-IFNa/RBV treatment regimens among subjects who (1) respond relatively poorly to the Peg-IFNalpha/RBV 4-week lead-in (e.g., <1 log10 IU/mL decline, greater than or equal to 1 log10 IU/mL to <2 log10 IU/mL decline, etc.), or (2) have an unfavorable IL28B genotype (if data are available). These pooled analyses should be conducted using data from the following completed and currently ongoing boceprevir clinical trials: P03523, P05216, P05101, P05411, P05685, and P06086. These analyses should be completed, and a study report submitted, within 9 months of collection of SVR outcome data from these clinical trials. Final Report Submission



PMR 1767-5 Conduct a study to analyze NS3/4A protease cleavage sites for the presence of boceprevir treatment-emergent substitutions for a selected subset of subjects (n~10) representative of the virologic failure responses and NS3 protease resistance patterns observed in Phase 3 trials. An additional subset of subjects (n~10) who experienced virologic failure, but for whom no clear resistance-associated substitutions in NS3/4A were detected, should also be analyzed for the presence of boceprevir treatment-emergent substitutions in NS3/4A protease cleavage sites. Final Report Submission

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PMR 1767-6 Report results from ongoing clinical trial P05063 regarding the long-term persistence of amino acid substitutions that emerged in boceprevir-treated subjects from the following Phase 2 and Phase 3 trials conducted to date: P03523, P03659, P05216 and P05101. For long-term, follow-up analyses of subjects from the Phase 3 trials (P05216 and P05101), if available, the same assay/vendor used initially to identify the treatment-emergent substitutions should continue to be used to monitor the persistence of the substitutions in the follow-up period. The persistence of detectable amino acid substitutions should be assessed for a treatment-free follow up period of approximately 2 years. Final Report Submission



PMR 1767-7 Conduct an in vivo drug-drug interaction trial between boceprevir and an oral contraceptive containing a progesterone component other than drospirenone. Final Report Submission


31-Mar-2012 Fulfilled

PMR 1767-8 Conduct an in vivo drug-drug interaction trial between boceprevir and methadone. Final Report Submission



PMR 1767-9 Conduct an in vivo drug-drug interaction trial between boceprevir and a sensitive substrate of p-glycoprotein (e.g. digoxin). Final Report Submission

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31-Aug-2016 Released

PMR 2034-1 Evaluate single-dose pharmacokinetics (PK) of boceprevir in treatment-naïve pediatric subjects 3 through 17 years of age to determine weight-based dosing for children that will result in exposures similar to those found to be safe and effective in adults. Using dose(s) selected based on the PK evaluation and agreed upon with the FDA, evaluate safety and treatment response of boceprevir in combination with pegylated interferon and ribavirin. Treatment response should be measured by sustained virologic response (SVR) in all pediatric subjects including previously untreated subjects and those who have failed a prior course of pegylated interferon and ribavirin therapy. Final Report Submission


31-Aug-2021 Released

PMR 2034-2 Collect long-term safety data for subjects enrolled in the pediatric boceprevir safety and treatment trial. Data collected should include at least 5 years of follow-up in order to characterize the long-term safety of boceprevir in pediatric patients, including growth assessment, sexual maturation and characterization of boceprevir resistance-associated substitutions in viral isolates from subjects failing therapy. Long-term Final Report Submission

ZEPATIER (grazoprevir (+) elbasvir)

31-Jan-2021 Ongoing

PMR 3008-1 Conduct a study to evaluate the pharmacokinetics, safety and treatment response (using sustained virologic response) of elbasvir and grazoprevir in pediatric subjects 3 to 17 years of age with chronic hepatitis C infection.

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31-Jul-2023 Ongoing

PMR 3008-2 Collect and analyze long-term safety data from pediatric subjects 3 to 17 years of age enrolled in the pediatric elbasvir and grazoprevir safety, pharmacokinetic and efficacy study. Data should be collected for at least 3 years following the end of treatment in order to characterize the long-term safety of elbasvir and grazoprevir including growth assessment, sexual maturation, and characterization of elbasvir and grazoprevir resistance associated substitutions in viral isolates from subjects failing therapy


31-Jan-2017 Ongoing

PMR 3008-3 Conduct site-directed mutant phenotype analyses of elbasvir against HCV replicons carrying the following NS5A substitutions: K24R (GT1a), H54Y (GT4d), E62D (GT1a), D427N (GT1a). Include cross-resistance analyses with approved NS5A inhibitors.


31-Jan-2017 Ongoing

PMR 3008-4 Conduct site-directed mutant phenotype analyses of grazoprevir against HCV replicons carrying the following NS3 substitutions: I48A/V (GT1a), T185S (GT1a/GT1b), E357G/K (GT1a). Include cross-resistance analyses with approved NS3/4A inhibitors

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31-Dec-2018 Ongoing

PMR 3008-5 Conduct a trial in hepatitis C virus genotype 1a infected subjects with at least one baseline NS5A polymorphism at amino acid position 28, 30, 31, or 93 to evaluate if treatment with elbasvir/grazoprevir and ribavirin for at least 16 weeks reduces the rate of virologic failure and the rate of treatment-emergent drug resistant viral populations. The trial should have adequate representation of subjects with baseline NS5A polymorphisms that have been demonstrated to have the greatest impact on elbasvir/grazoprevir efficacy in clinical trials evaluating recommended regimens.

ZERBAXA™ (ceftolozane sulfate (+) tazobactam sodium)

31-Dec-2020 Pending

PMR 2809-1 Conduct a randomized, double-blind, multicenter, comparative study to establish the safety and tolerability profile of ceftolozane/tazobactam compared to that of meropenem in hospitalized children from birth to <18 years with cUTI. The dose for this study will be determined upon review of the data to be submitted by December 2016 from a single-dose, multicenter, non-comparative study assessing the pharmacokinetics (PK) of ceftolozane/tazobactam in pediatric patients ages 0 to <18 years that was initiated in June 2014. Final Report Submission

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31-Dec-2020 Pending

PMR 2809-2 A randomized, double-blind, multicenter, comparative study to establish the safety and tolerability profile of ceftolozane/tazobactam compared to that of meropenem in hospitalized children from birth to <18 years with cIAI. The dose from this study will be determined upon review of the data to be submitted by December 2016 from the a single-dose, multicenter, non-comparative study to assessing the PK pharmacokinetics (PK) of ceftolozane/tazobactam in pediatric patients ages 0 to <18 years that was initiated in June 2014. Final Report Submission


31-May-2020 Ongoing

PMR 2809-3 Conduct a prospective study over a five-year period after the introduction of ZERBAXA (ceftolozane/tazobactam) to the market to determine if decreased susceptibility of ZERBAXA (ceftolozane/tazobactam) is occurring in the target population of bacteria that are in the approved ZERBAXA (ceftolozane/tazobactam) label. Final Report Submission

ZETIA (ezetimibe)


PMR 1806-1 Pediatric Plan in Adolescents at High Risk for Cardiovascular Disease with Primary Hypercholesterolemia. Final Report Submission

ZINPLAVA (bezlotoxumab)

30-Nov-2022 Pending

PMR 3118-1 Conduct a randomized, double-blind, placebo-controlled trial of safety, efficacy, and pharmacokinetics of Zinplava (bezlotoxumab) in pediatric patients from 1 to less than 18 years of age receiving antibacterial therapy for C. difficile infection. Final report submission.

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status as of 06-jan-2017 status explanation of status pmr ... · pmr 2149-1 a 12-week, randomized,...

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