Drug-drug Interaction (DDI) Rifabutin

NCT02138084 | Completed Phase 1

• 2 other identifiers: 206282AI438-041
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to provide dosing recommendations for the coadministration of BMS-663068 and Rifabutin with and without Ritonavir in upcoming Phase 3 studies and for prescribing information purposes

Conditions

Infection, Human Immunodeficiency Virus

Outcome Measures

Primary Outcomes (2)

• Maximum observed plasma concentration (Cmax) of BMS-626529

  Day 2 to Day 15

• Area under the concentration-time curve in 1 dosing interval [AUC(TAU)] of BMS-626529

  Day 2 to Day 15

Secondary Outcomes (4)

• Time of maximum observed plasma concentration (Tmax) of BMS-626529

  Day 2 to Day 15

• Concentration at 12 hours after dosing (C12) of BMS-626529

  Day 2 to Day 15

• Trough observed plasma concentration (Ctrough) of BMS-626529 (predose)

  Day 2 to Day 15

• Safety and tolerability include incidence of adverse events (AEs), serious AEs (SAEs), AEs leading to discontinuation, deaths, marked laboratory abnormalities, and abnormalities in vital signs, physical examination, and 12-lead electrocardiograms (ECGs)

  Up to Day 30 after discontinuation of dose (approximately 45 days)

Study Arms (2)

Cohort 1: BMS-663068 + Rifabutin

EXPERIMENTAL

Regimen A: BMS-663068 tablet by mouth as specified Regimen B: BMS-663068 tablet with Rifabutin capsule by mouth as specified

Drug: BMS-663068; Drug: Rifabutin

Cohort 2: BMS-663068 + Rifabutin + Ritonavir

EXPERIMENTAL

Regimen A: BMS-663068 tablet by mouth as specified Regimen C: BMS-663068 tablet, Rifabutin capsule and Ritonavir (RTV) capsule by mouth as specified

Drug: BMS-663068; Drug: Rifabutin; Drug: Ritonavir

Interventions

BMS-663068 DRUG

BMS-663068

Cohort 1: BMS-663068 + Rifabutin; Cohort 2: BMS-663068 + Rifabutin + Ritonavir

Rifabutin DRUG

Rifabutin

Cohort 1: BMS-663068 + Rifabutin; Cohort 2: BMS-663068 + Rifabutin + Ritonavir

Ritonavir DRUG

Ritonavir

Cohort 2: BMS-663068 + Rifabutin + Ritonavir

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Signed Written Informed Consent
• a) Signed written informed consent must be obtained from the subjects in accordance with requirements of the study center's Institutional Review Board (IRB) or Independent Ethics Committee (IEC) before the initiation of any protocol-required procedures
• Target Population
• a) Healthy subjects as determined by no clinically significant deviation from normal in medical history, physical examination findings, 12-lead ECG measurements, and clinical laboratory test results
• b) Body mass index (BMI) of 18.0 to 32.0 kg/m2, inclusive BMI = weight (kg)/\[height (m)\]2
• c) Subject Reenrollment: This study permits the reenrollment of a subject that has discontinued the study as a pretreatment failure (ie, subject has not been randomized/has not been dosed). If reenrolled, the subject must be reconsented
• Age and Reproductive Status
• a) Men and women, ages 18 to 50 years, inclusive
• b) Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) within 24 hours prior to the start of study drug
• c) Women must not be breastfeeding
• d) WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment plus 5 half-lives of Rifabutin (13 days) plus 30 days (duration of ovulatory cycle) for a total of 43 days posttreatment completion
• e) Men who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment plus 5 half-lives of Rifabutin (13 days) plus 90 days (duration of sperm turnover) for a total of 103 days posttreatment completion

You may not qualify if:

• Medical History and Concurrent Diseases
• a) Any significant acute or chronic medical illness as determined by the Investigator.
• b) Current or recent (within 3 months of study drug administration) gastrointestinal disease
• c) Any major surgery within 4 weeks of study drug administration
• d) Any gastrointestinal surgery that could impact upon the absorption of study drug
• e) Intractable diarrhea (≥6 loose stools per day for at least 7 consecutive days) within 30 days prior to the first dose of study drug
• f) History of acute or chronic pancreatitis
• g) History of active or latent tuberculosis or any recent exposure to someone with tuberculosis
• h) History of uveitis and/or current eye or vision problems with the exception of corrective lenses
• i) Contact lens use during study drug administration or the need for contact lenses during study drug administration
• j) Donation of blood to a blood bank or in a clinical study (except screening visit) within 4 weeks of study drug administration (within 2 weeks for plasma donation only)
• k) Blood transfusion within 4 weeks of study drug administration.
• l) History of any hemolytic disorders, including drug-induced hemolysis.
• m) Inability to tolerate oral medication
• n) Inability to be venipunctured and/or tolerate venous access

Sponsors & Collaborators

• ViiV Healthcare: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

GSK Investigational Site

Austin, Texas, 78744, United States

Location

MeSH Terms

Conditions

Infections; Acquired Immunodeficiency Syndrome

Interventions

fostemsavir; Rifabutin; Ritonavir

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring

Study Officials

• GSK Clinical Trials

  ViiV Healthcare

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2014
• First Posted: May 14, 2014
• Study Start: May 14, 2014
• Primary Completion: July 24, 2014
• Study Completion: July 24, 2014
• Last Updated: September 25, 2017

Record last verified: 2017-09

Locations

US (1)