Postmarketing Requirements and Commitments - U.S.

When the U.S. Food and Drug Administration grants marketing approval to a new drug or biologic, it may condition that approval on the sponsor’s commitment to conduct certain future studies and clinical trials, in order to generate additional useful data on the safety, efficacy or optimal use of the medicine. Some of these studies and clinical trials may be required. This website provides information on Bristol-Myers Squibb’s U.S. postmarketing requirements and commitments. These studies build on the data that was submitted for approval.

The data available on this site includes:

  • Product (generic and trade name)
  • Description of the Requirement or Commitment
  • Projected Completion Date
  • Study Status
  • Relevant or explanatory notes, if any

Differences may be noted between the status of a requirement or commitment reported here compared to the status as reported on the FDA website. This is usually a result of the fact that the FDA requires time to review the data, as well as update its website.

The Bristol-Myers Squibb website focuses on clinical and other studies related to the safety, efficacy and use of the medicine. It does not list commitments related to manufacturing issues, known as “Chemistry, Manufacturing and Controls”. Also, this site lists commitments only for those products Bristol-Myers Squibb is the sponsor holding the U.S. regulatory approval for the medicine.

This site will be updated twice/year to reflect the most current information. Once the FDA determines that a requirement or commitment is fulfilled or they release the company from its commitment, it will be removed from the website.

U.S. Postmarketing Requirement and Commitment Studies


Abatacept

Generic Name
ABATACEPT
Trade Name
ORENCIA
Projected Completion Date
31-Dec-16
Study Status
Submitted

Description of Commitment

Protocol IM101045A, a pharmacoepidemiology study to assess the short term (2 years) and potential long term (4 years) risk of hospitalization due to infection (all hospitalized infections, hospitalized pneumonia, and all opportunistic infections) among patients with RA treated with Abatacept in comparison to other DMARDs within a large cohort of individuals with commercial health insurance. This study will also characterize patients receiving Abatacept and monitor any off-label use.

Generic Name
ABATACEPT
Trade Name
ORENCIA
Projected Completion Date
31-Dec-16
Study Status
Submitted

Description of Commitment

Protocol IM101045B, proposed as an observational prospective pharmacoepidemiology cohort study to assess the short and long-term risk of malignancies and infection in patients with RA treated with Abatacept in comparison to other DMARDs within an existing registry containing patients with rheumatoid arthritis. Follow-up will be for at least 5 years after the last patient is enrolled.

Generic Name
ABATACEPT
Trade Name
ORENCIA
Projected Completion Date
30-Jun-29
Study Status
Ongoing

Description of Commitment

Submission of the protocol, interim reports, and final study report for a JIA patient safety registry comprised of at least 500 patients. This protocol should include a plan for more intensive scrutiny for the first 3 years, with annual follow ups (which could be telephonic) assessing for occurrence of malignancies, other autoimmune diseases, and serious infections, for a total of 10 years. Patients turning 18 years of age or older should continue to be followed until they have completed the 10 year follow-up period. Information on these patients may be obtained via annual questionnaire/ telephonic follow-up with attention to key adverse events rather than full clinic visit with examination. Protocol Submission: December 31, 2008; Study Start: June 30, 2009; Interim Report Submissions: June 30, 2014/2019/2024; Final Report Submission: June 30, 2029.

Generic Name
ABATACEPT
Trade Name
ORENCIA
Projected Completion Date
31-Jan-18
Study Status
Ongoing

Description of Commitment

Conduct a PK/safety study of SC abatacept in polyaricular JIA patients ages 6 to 17 years of age.


Apixaban

Generic Name
APIXABAN
Trade Name
ELIQUIS
Projected Completion Date
31-Jul-18
Study Status
Ongoing

Description of Commitment

Assess apixaban pharmacokinetics and pharmacodynamics in approximately 50 pediatric subjects aged 0 to less than 18 years, who are at risk for a venous or arterial thrombotic disorder, to determine dosing requirements for subsequent studies in children. Completion and submission of results of Study CV185118 and available data from CV185079 may be used to fulfill this requirement.

Generic Name
APIXABAN
Trade Name
ELIQUIS
Projected Completion Date
17-Apr-21
Study Status
Ongoing

Description of Commitment

Conduct a randomized, open-label, active-controlled, safety and descriptive efficacy study to assess apixaban treatment in 150 pediatric patients evaluable for efficacy and safety, aged 0 to less than 18 years, requiring anticoagulation for the treatment of a venous thromboembolic event (VTE). This trial will also evaluate apixaban pharmacokinetics, anti-Factor Xa activity, and imaging assessment of clot status at the end of treatment in pediatric patients requiring anticoagulation for the treatment of a VTE. Completion and submission of results of Study CV185325 may be used to fulfill this requirement.


 Atazanavir / Cobicistat

Generic Name
ATAZANAVIR/ COBICISTAT
Trade Name
EVOTAZ
Projected Completion Date
28-Feb-19
Study Status
Pending

Description of Commitment

Evaluate the pharmacokinetics, safety, and antiviral activity (efficacy) of atazanavir and cobicistat fixed-dose combination (FDC) age-appropriate formulation in HIV-infected pediatric subjects 3 months to less than 3 years of age. The safety and antiviral activity (efficacy) of atazanavir and cobicistat FDC age-appropriate formulation in pediatric subjects should be evaluated for a minimum of 24 weeks. A clinical trial in children 3 months to less than 3 years of age may not be required if the dosing recommendation for the FDC age-appropriate formulation can be supported by pediatric trials already conducted with the individual drug products and if the age-appropriate FDC produces similar exposures as the individual components.

Generic Name
ATAZANAVIR/ COBICISTAT
Trade Name
EVOTAZ
Projected Completion Date
28-Feb-19
Study Status
Pending

Description of Commitment

Evaluate the pharmacokinetics, safety, and antiviral activity (efficacy) of atazanavir and cobicistat fixed-dose combination (FDC) age-appropriate formulation in HIV-infected pediatric subjects 3 years to less than 6 years of age. The safety and antiviral activity (efficacy) of atazanavir and cobicistat FDC age-appropriate formulation in pediatric subjects should be evaluated for a minimum of 24 weeks. A clinical trial in children 3 years to less than 6 years of age may not be required if the dosing recommendation for the FDC age-appropriate formulation can be supported by pediatric trials already conducted with the individual drug products and if the age-appropriate FDC produces similar exposures as the individual components.

Generic Name
ATAZANAVIR/ COBICISTAT
Trade Name
EVOTAZ
Projected Completion Date
28-Feb-19
Study Status
Pending

Description of Commitment

Evaluate the pharmacokinetics, safety, and antiviral activity (efficacy) of atazanavir and cobicistat fixed-dose combination (FDC) age-appropriate formulation in HIV-infected pediatric subjects 6 years to less than 12 years of age. The safety and antiviral activity (efficacy) of atazanavir and cobicistat FDC age-appropriate formulation in pediatric subjects should be evaluated for a minimum of 24 weeks. A clinical trial in children 6 years to less than 12 years of age may not be required if the dosing recommendation for the FDC age-appropriate formulation can be supported by pediatric trials already conducted with the individual drug products and if the age-appropriate FDC produces similar exposures as the individual components.

Generic Name
ATAZANAVIR/ COBICISTAT
Trade Name
EVOTAZ
Projected Completion Date
28-Feb-19
Study Status
Pending

Description of Commitment

Evaluate the pharmacokinetics, safety, and antiviral activity (efficacy) of atazanavir and cobicistat fixed-dose combination (FDC) age-appropriate formulation in HIV-infected pediatric subjects 12 years to less than 18 years of age. The safety and antiviral activity (efficacy) of atazanavir and cobicistat FDC age-appropriate formulation in pediatric subjects should be evaluated for a minimum of 24 weeks. A clinical trial in children 12 years to less than 18 years of age may not be required if the dosing recommendation for the FDC age-appropriate formulation can be supported by pediatric trials already conducted with the individual drug products and if the age-appropriate FDC produces similar exposures as the individual components.


Belatacept

Generic Name
BELATACEPT
Trade Name
NULOJIX
Projected Completion Date
30-Apr-20
Study Status
Ongoing

Description of Commitment

Conduct a prospective, observational study utilizing data from the United Network for Organ Sharing (UNOS) on the pattern of belatacept use in US adult kidney-only transplant recipients at transplant and one year post-transplant. Specifically, the study will assess the prevalence of belatacept use and the characteristics of belatacept users, as related to the risk of PTLD, including Epstein-BarrVirus (EBV) and cytomegalovirus (CMV) serostatus. In addition, the study will collect information on adult kidney-only transplant recipients who switch to or from belatacept within one year post-transplant. (Protocol Number IM103074).

Generic Name
BELATACEPT
Trade Name
NULOJIX
Projected Completion Date
30-Apr-20
Study Status
Ongoing

Description of Commitment

Conduct a prospective observational study utilizing data from the United Network for Organ Sharing (UNOS) on the incidence rates of post-transplant lymphoproliferative disorder (PTLD) in US adult kidney-only transplant recipients who are treated with belatacept compared to recipients treated with calcineurin inhibitor (CNI)-based regimens. Recipient characteristics will be collected, including EBV and CMV serostatus, location of the PTLD, and outcome (survival or mortality). Incidence rates of PTLD in belatacept-exposed patients will be quantified beginning when 500 belatacept-exposed patients have at least 1 year of follow-up. Relative risks of PTLD for belatacept compared to CNI-based regimens will be estimated after 1,000 person years have been accumulated in transplant recipients initiated on belatacept at transplantation. (Protocol Number IM103075).

Generic Name
BELATACEPT
Trade Name
NULOJIX
Projected Completion Date
30-Apr-20
Study Status
Ongoing

Description of Commitment

Conduct a prospective registry of belatacept use in US adult kidney-only transplant recipients to determine the incidence rates of post-transplant lymphoproliferative disorder PTLD, PTLD in the central nervous system (CNS PTLD), and progressive multifocal leukoencephalopathy (PML) in US adult EBV seropositve kidney transplant recipients treated with belatacept in clinical practice. All US adult kidney transplant centers dispensing belatacept will be asked to participate in the study (i.e., if a center does not respond or declines to participate, the reason(s) for nonparticipation will be identified and documented). Recipient characteristics will be collected, including EBV and CMV serostatus, timing of initiation of belatacept in relation to the transplant, location of the PTLD, and outcome (survival or mortality). (Protocol Number IM13076).


Daclatasvir

Generic Name
DACLATASVIR
Trade Name
DAKLINZA
Projected Completion Date
31-Dec-23
Study Status
Released

Description of Commitment

Conduct a study to evaluate the pharmacokinetics, safety and treatment response (using sustained virologic response) of daclatasvir in combination with other direct acting antivirals in pediatric subjects 3 through 17 years of age with chronic hepatitis C.

Generic Name
DACLATASVIR
Trade Name
DAKLINZA
Projected Completion Date
29-Feb-16
Study Status
Submitted

Description of Commitment

Evaluate the potential mechanism of both pharmacodynamic and pharmacokinetic interactions between amiodarone and HCV direct acting antivirals, including daclatasvir, using a multielectrode array electrophysiology study in human stem-cell derived cardiomyocytes.

Generic Name
DACLATASVIR
Trade Name
DAKLINZA
Projected Completion Date
29-Feb-16
Study Status
Submitted

Description of Commitment

Evaluate the effect of individual HCV direct acting antivirals including daclatasvir on the plasma protein binding of amiodarone using the TRANSIL high sensitivity binding assay to help elucidate the potential mechanism of an interaction between amiodarone and HCV direct acting antivirals.

Generic Name
DACLATASVIR
Trade Name
DAKLINZA
Projected Completion Date
30-Nov-17
Study Status
Ongoing

Description of Commitment

Conduct a trial in hepatitis C virus genotype 3 infected subjects with cirrhosis treated with daclatasvir plus sofosbuvir to determine if a longer duration of treatment or the addition of ribavirin reduces the rate of virologic failure and the rate of treatment-emergent drug resistant viral populations.

Generic Name
DACLATASVIR
Trade Name
DAKLINZA
Projected Completion Date
31-Dec-23
Study Status
Released

Description of Commitment

Conduct a study to evaluate the pharmacokinetics, safety and treatment response (using sustained virologic response) of daclatasvir in combination with other direct acting antivirals in pediatric subjects 3 through 17 years of age with chronic hepatitis C.


Efavirenz

Generic Name
EFAVIRENZ
Trade Name
SUSTIVA
Projected Completion Date
29-Feb-16
Study Status
Fulfilled

Description of Commitment

Conduct a trial to quantify efavirenz QT prolongation in CYP2B6*6 homozygous and heterozygous subjects.


Elotuzumab 

Generic Name
ELOTUZUMAB
Trade Name
EMPLICITI
Projected Completion Date
31-Mar-17
Study Status
Ongoing

Description of Commitment

Conduct an elotuzumab exposure-response analysis for efficacy and safety utilizing data from trial CA204006. The result of the exposure-response analyses from both CA204004 and CA204006 will be used to determine whether a post-marketing trial is needed to optimize the dose in patients with multiple myeloma who have low exposure to elotuzumab at the approved dose (10 mg/kg). Submit a final report of the exposure-response analyses based on CA204004 and CA 204006.


Entecavir

Generic Name
ENTECAVIR
Trade Name
BARACLUDE
Projected Completion Date
6-Jul-16
Study Status
Delayed
Notes
Delay due to additional time needed to obtain and incorporate feedback into study protocol.

Description of Commitment

Conduct and submit a final study report for a large simple safety study to assess the major clinical outcomes of death, progression of liver disease, and cancer in a broad population of HBV-infected patients using entecavir compared to standard of care over a period of 5 to 10 years of follow-up. The study should be randomized, stratified according to prior treatment, and of sufficient size to detect a 30% difference in cancer outcomes between the two groups. Monitoring by an independent Data Safety Monitoring Board is recommended. Given the anticipated length of the study, it is recommended that the protocol include plans to assess the adequacy of enrollment and submit interim reports of results at yearly intervals.

Generic Name
ENTECAVIR
Trade Name
BARACLUDE
Projected Completion Date
31-Dec-15
Study Status
Delayed
Notes
Delay due to company decision to repeat genotyping testing to support the most robust assessment possible.

Description of Commitment

Submit integrated analyses for genotypic and phenotypic resistance for studies AI463048, AI463050, AI463085, AI463901, AI463110, and AI463111, and integrated phenotypic resistance analyses for studies AI463028 and AI463189 in SAS format. The virology data should be submitted following the guidance format.


Ipilimumab

Generic Name
IPILIMUMAB
Trade Name
YERVOY
Projected Completion Date
29-Dec-17
Study Status
Ongoing

Description of Commitment

To conduct an assessment of anti-drug antibody (ADA) response and neutralizing ADA responses to ipilimumab with a validated assay (required in PMR 2 and 3) capable of sensitively detecting ADA responses in the presence of ipilimumab levels that are expected to be present at the time of patient sampling. The ADA response will be evaluated in at least 300 ipilimumab-treated patients enrolled in the required postmarketing trial (PMR 6) comparing 3 mg/kg versus 10 mg/kg of ipilimumab monotherapy. The final report will include information on the level of ipilimumab in each patient's test sample at each sampling time point.

Generic Name
IPILIMUMAB
Trade Name
YERVOY
Projected Completion Date
29-Dec-16
Study Status
Submitted

Description of Commitment

During the conduct of the required postmarketing trial comparing 3mg/kg vs.10mg/kg ipilimumab monotherapy (PMR 6), you will obtain comprehensive baseline DNA sample acquisition (≥ 95% of ITT) and conduct pharmacogenomic association analyses to assess the potential clinical utility of CD86 gene polymorphisms as genetic determinants of immune mediated adverse events. You will provide a protocol that addresses SNP selection, data analyses approaches, and other methodological issues. You will provide a Final Report including electronic datasets.

Generic Name
IPILIMUMAB
Trade Name
YERVOY
Projected Completion Date
31-Dec-17
Study Status
Ongoing

Description of Commitment

Following the assessment of data from Trial CA184024, you will design and conduct a trial to compare the efficacy, with the primary endpoint of overall survival and the safety of ipilimumab at doses of 3mg/kg versus 10mg/kg given as monotherapy every three weeks for four doses in patients with unresectable Stage III or Stage IV melanoma.

Generic Name
IPILIMUMAB
Trade Name
YERVOY
Projected Completion Date
31-Dec-18
Study Status
Ongoing

Description of Commitment

To identify further genetic determinants of immune-mediated adverse events caused by ipilimumab. DNA samples from the required postmarketing study comparing 3 mg/kg vs. 10 mg/kg ipilimumab monotherapy will be used to conduct genome-wide association analyses. The design of these analyses will be reviewed by FDA and a final report with electronic datasets will be provided.

Generic Name
IPILIMUMAB
Trade Name
YERVOY
Projected Completion Date
31-May-24
Study Status
Ongoing

Description of Commitment

Conduct a Pregnancy Pharmacovigilance Study to evaluate pregnancy outcomes and infant outcomes following exposure to Yervoy (ipilimumab). This study will include a mechanisn to collect, classify, and analyze data on direct exposures (women exposed to ipilimumab as treatment). There will be interim annual reporting of the data collected from the study. The study, at a minimum, will include the following key elements: Data collection of prospective and retrospective data points, adequate to produce informative, reliable data outcomes; Data analysis utilizing descriptive statistics for summarizing data that will fully capture outcomes of concern. Data collected prospectively will be analyzed separately from data collected retrospectively; Description of procedures including patient recruitment, along with healthcare provider awareness of the potential safety risk and existence of this study, and the monitoring of pregnancy and infant outcomes.

Generic Name
IPILIMUMAB
Trade Name
YERVOY
Projected Completion Date
31-Dec-19
Study Status
Ongoing

Description of Commitment

Submit the final clinical report and datasets at the time of final analysis for overall survival (OS) of Trial CA184029, entitled "Adjuvant immunotherapy with anti-CTLA-4 monoclonal antibody (ipilimumab) versus placebo after complete resection of high-risk Stage III melanoma: A randomized, double-blind Phase 3 trial of the EORTC Melanoma Group," to inform the product label with mature OS data.

Generic Name
IPILIMUMAB
Trade Name
YERVOY
Projected Completion Date
30-Apr-21
Study Status
Ongoing

Description of Commitment

Submit the final clinical report and datasets of Trial E1609, entitled "A Phase III Randomized Study of Adjuvant Ipilimumab Anti-CTLA4 Therapy Versus High Dose Interferon a-2b for Resected High Risk Melanoma" to inform any change to the recommended dose of Yervoy (ipilimumab) for adjuvant treatment of resected Stage III melanoma patients, if required, based on the final results of Trial E1609.


Nivolumab

Generic Name
NIVOLUMAB
Trade Name
OPDIVO
Projected Completion Date
31-Dec-16
Study Status
Submitted

Description of Commitment

Conduct and submit the results of a multicenter, randomized trial or trials establishing the superiority of nivolumab over standard therapy in adult patients with unresectable or metastatic melonoma who are refractory to ipilimumab or who have not been previously treated with ipilimumab.

Generic Name
NIVOLUMAB
Trade Name
OPDIVO
Projected Completion Date
31-Dec-15
Study Status
Fulfilled

Description of Commitment

Conduct a randomized trial that will characterize the incidence, severity and response to treatment of nivolumab induced immune-mediated adverse reactions to include immune-mediated pneumonitis.

Generic Name
NIVOLUMAB
Trade Name
OPDIVO
Projected Completion Date
31-Dec-15
Study Status
Fulfilled

Description of Commitment

Submit the final report and efficacy datasets for the open-label randomized trial of nivolumab versus docetaxel in patients with previously treated advanced squamous non-small cell lung cancer.

Generic Name
NIVOLUMAB
Trade Name
OPDIVO
Projected Completion Date
31-Jul-15
Study Status
Submitted

Description of Commitment

Conduct and submit the results of a multicenter, randomized trial or trials to verify and describe the clinical benefit of nivolumab in combination with ipilimumab in previously untreated adult patients with unresectable or metastatic, BRAF V600 wild-type melanoma.

Generic Name
NIVOLUMAB
Trade Name
OPDIVO
Projected Completion Date
31-Dec-21
Study Status
Ongoing

Description of Commitment

An Enhanced Pharmacovigilance Study to evaluate the risks factors and clinical sequelae of immune-mediated encephalitis following exposure to OPDIVO (nivolumab). This study will include a mechanism to collect, classify, and analyze data on moderate to severe neurologic deterioration in patients exposed to OPDIVO (nivolumab). The study at a minimum will include the following key elements: a. Data collection of retrospective data points including Brain imaging, specifically magnetic resonance imaging (MRI) with and without gadolinium contrast, and with diffusion weighted imaging (DWI). Results of lumbar puncture including: Cell counts, protein, glucose; Viral encephalitis panel; JC virus detection; Autoimmune/ paraneoplastic encephalitis panel. Results of serum studies including: JC virus detection, Autoimmune/ paraneoplastic encephalitis panel, Vitamin deficiency studies [thiamine, niacin, and B12]. Results of complete neurologic examinations. Concomitant medication use, including use of steroids or other immunemodulating therapies. b. Data analysis utilizing descriptive statistics for summarizing data that will fully capture the outcome of concern.

Generic Name
NIVOLUMAB
Trade Name
OPDIVO
Projected Completion Date
31-Mar-16
Study Status
Submitted

Description of Commitment

Evaluate the impact of anti-drug-antibody on the safety and efficacy of nivolumab in Trial CA209025, and submit the report. Trial CA209025 is entitled, “A
Randomized, Open-label, Phase 3 Study of Nivolumab versus Everolimus in Subjects with Advanced or Metastatic Clear Cell Renal Cell Carcinoma who Have Received Prior Anti-angiogenic Therapy."

Generic Name
NIVOLUMAB
Trade Name
OPDIVO
Projected Completion Date
31-Dec-16
Study Status
Submitted

Description of Commitment

Submit the final overall survival (OS) data from Trial CA209037, a randomized, open-label, Phase 3 Trial of Nivolumab Versus Investigator's Choice in Advanced (Unresectable or Metastatic) Melonoma Patients Progressing Post Anti-CTLA-4 Therapy, to provide long-term data that will inform the label on the efficacy of nivolumab as a treatment for patients with unresectable or metastatic melonoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor.

Generic Name
NIVOLUMAB
Trade Name
OPDIVO
Projected Completion Date
31-Dec-26
Study Status
Ongoing

Description of Commitment

Conduct a randomized phase 3 clinical trial in classical Hodgkin lymphoma that verifies and isolates the clinical benefit of nivolumab for patients with classical Hodgkin lymphoma. The primary endpoint would be progression-free survival as determined by an independent review committee. Overall survival would be a key secondary endpoint.

Generic Name
NIVOLUMAB
Trade Name
OPDIVO
Projected Completion Date
31-Dec-22
Study Status
Ongoing

Description of Commitment

Characterize complications after allogeneic hematopoietic stem cell transplantation (HSCT) following nivolumab in at least 90 patients with classical Hodgkin lymphoma, of which at least 50% have received nivolumab alone or in combination as the regimen immediately prior to the allogeneic HSCT conditioniing regimen. Evaluate toxicities at least through transplant Day 180, and include details of prior nivolumab treatment and the transplant regimen. Characterize toxicities including hyperacute graft-versus-host disease (GVHD), severe (grade III-IV) acute GVHD, febrile syndromes treated with steroids, immune mediated adverse events, pulmonary complications, hepatic veno-occlusive disease, critical illness, and transplant-related mortality. Toxicities may be characterized prospectively, or through a combination of prospective and retrospective data analysis.