Study to Evaluate the Pharmacodynamics, Safety and Pharmacokinetics of BMS-955176 and BMS-955176 with Atazanavir +/- Ritonavir in HIV-1 Infected Subjects

• Conditions: Human Immunodeficiency Virus Type-1 (HIV-1) infection; MedDRA version: 16.1Level: LLTClassification code 10068341Term: HIV-1 infectionSystem Organ Class: 100000004862; Therapeutic area: Diseases [C] - Virus Diseases [C02]

• Registration Number: EUCTR2012-004124-38-DE
• Lead Sponsor: Bristol-Myers Squibb International Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-12-27
• Last Update Posted: 16 November 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1) Signed Written Informed Consent: The signed informed consent form.
2) Target Population
a) HIV-1 infected (clades B or C) subjects meeting the following criteria at the screening visit (within 30 days of enrollment):
i) Plasma HIV-1 RNA = 5,000 copies/mL (may be repeated for confirmation)
ii) Antiretroviral treatment naive (defined as <1 week of ARV treatment) or ART-experienced (protease inhibitor and/or maturation inhibitor naive)
iii) Subjects are not eligible for HIV-1 treatment based on the United States Department of Health and Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents or have declined initiation of cART
iv) CD4+ lymphocyte measurement = 200 cells/µL (may be repeated for confirmation)
v) In Parts A and B, all subjects are infected with clade B HIV-1 virus
vi) In Part C, all subjects are infected with clade C HIV-1 virus
b) Body Mass Index (BMI) of 18.0 to 35.0 kg/m2, inclusive. BMI = weight (kg)/m2
c) Subject Re-enrollment: This study permits the re-enrollment of a subject that has discontinued the study as a pre-treatment failure (ie, subject has not been randomized / has not been treated). If re-enrolled, the subject must be reconsented and re-numbered.
3) Age and Reproductive Status
a) Men and women, ages 18-55 years, inclusive for Parts A and C
b) Men, ages 18-55 years, inclusive for Part B
c) In Parts A and C, women of childbearing potential (WOCBP) must use method(s) of contraception based on the tables in Appendix 1. Because BMS-955176 may be a selective developmental toxicant and a potential teratogen, subjects must agree to the use of two methods of contraception, one method being highly effective and the other method being highly effective or less effective as defined in Appendix 1. The individual methods of contraception and duration should be determined in consultation with the investigator. WOCBP must follow instructions for birth control when the half life of the investigational drug is greater than 24 hours, contraception should be continued for a period of 30 days plus the time required for the investigational drug to undergo five half lives (a total of 38 days post the last dose). In addition, WOCBP must follow the methods of contraception at least 4 weeks prior to the first dose and during the treatment.
d) In Parts A and C, women must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of investigational product.
e) In Parts A and C, women must not be breastfeeding
f) Men who are sexually active with WOCBP must use two methods of contraception, one method being highly effective and the other method being highly effective or less effective (listed in Appendix 1). The investigator shall review contraception methods and the time period that contraception must be followed. Men that are sexually active with WOCBP must follow instructions for birth control when the half life of the investigational drug is greater than 24 hours, contraception should be continued for a period of 90 days plus the time required for the investigational drug to undergo five half lives (for a total of 98 days post the last dose).
g) Women who are not of childbearing potential (ie, who are postmenopausal or surgically sterile; see Section 3.3.3 for the definition of WOCBP) and azoospermic men do not require contraception.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2

Exclusion Criteria

1) Target Disease Exceptions
a) History of genotypic and/or phenotypic drug resistance testing showing resistance to protease inhibitors
i) Screening HIV-1 genotypic drug resistance testing at baseline showing primary protease inhibitor resistance mutations as defined by the presence of any of the following: D30N, M46I/L, I47V/A, G48V, I50L, I54M/L, Q58E, T74P, L76V, V82A/F/L/T/S, N83D, I84V, N88S, L90M
2) Medical History and Concurrent Diseases
a) Any significant acute or chronic medical illness which is not stable or is not controlled with medication or not consistent with HIV-1 infection.
b) Current or recent (within 3 months of study drug administration) gastrointestinal disease that, in the opinion of the Investigator or Medical Monitor, may impact on drug absorption.
c) Any major surgery within 4 weeks of study drug administration.
d) Acute diarrhea lasting = 1 day, within 3 weeks prior to randomization. Diarrhea will be defined as the passage of liquid feces and/or a stool frequency greater than three times per day.
e) Subjects with history of Gilbert’s syndrome.
f) Subjects with antiretroviral treatment within 12 weeks prior to screening
g) Subjects currently co-infected with hepatitis C or hepatitis B
h) Subjects previously received an HIV maturation inhibitor or HIV protease inhibitor
i) A personal history of clinically relevant cardiac disease, symptomatic or asymptomatic arrhythmias, syncopal episodes, or additional risk factors for torsades de pointes. A personal or family history of long QT syndrome.
j) Subjects who are unwilling to practice adequate infection protection during and after study participation to minimize potential for spread of HIV infection, including HIV which may have developed resistance to HIV maturation inhibitor and/or ATV. Such protections could include, but are not limited to behaviors to minimize potential for exposure to the subjects’ bodily fluids or initiation of cART therapy if indicated and recommended by a physician.
k) Any gastrointestinal surgery that could impact upon the absorption of study drug.
l) Donation of blood to a blood bank or in a clinical study (except a screening visit) within 4 weeks of study drug administration (within 2 weeks for plasma only).
m) Blood transfusion within 4 weeks of study drug administration.
n) Inability to tolerate oral medication.
o) Inability to be venipunctured and/or tolerate venous access.
p) Smoking more than 10 cigarettes per day.
q) Recent (within 6 months of study drug administration) drug or alcohol abuse as defined in DSM IV, Diagnostic Criteria for Drug and Alcohol Abuse (Appendix 2).
r) Any other sound medical, psychiatric and/or social reason as determined by the investigator.
3) Physical and Laboratory Test Findings
a) Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG or clinical laboratory determinations or not consistent with the subject’s degree of HIV infection.
b) Any of the following on 12-lead electrocardiogram (ECG) prior to study drug administration, confirmed by repeat.
i) PR = 210 msec
ii) QRS = 120 msec
iii) QT = 500 msec
iv) QTcF = 470 msec for women and = 450 msec for men
c) Evidence of second or third degree heart block prior to study drug, confirmed by repeat ECG.
d) Positive urine screen for drugs of abuse at either Screening or Day -1 without a valid prescription (subjects positive for cannabinoids and/or amphetamines wi

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified