Study to Evaluate the Pharmacokinetics and Safety of INX-08189 Administered With VictrelisTM in Healthy Subjects

NCT01471717 | Completed Phase 1 DMC

• 2 other identifiers: AI472-004INX-189-004
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed to evaluate the potential for a pharmacokinetic drug-drug interaction between INX-08189 and Victrelis, a Direct Acting Antiviral (DAA).

Conditions

Healthy

Keywords

PK; pharmacokinetics; INX08189; Victrelis; Inhibitex

Outcome Measures

Primary Outcomes (2)

• PK parameters of INX-08189, INX-08032, and Victrelis when dosed alone and in combination

  PK parameters of INX-08189, INX-08032, and Victrelis when dosed alone and in combination: maximum observed plasma concentration (Cmax), time at which Cmax is observed (Tmax), plasma concentration at the end of dosing interval (Ctau), area under the plasma concentration-time curve from time 0 to the end of dosing interval (AUC0-tau), elimination half-life (t1/2), apparent oral clearance (CL/F), and apparent oral volume of distribution (Vz/F), as applicable

  INX-08189: C1: Days 4 & 7; C2: Day 7 pre-dose & 15, 30, & 45 minutes, & 1, 2, 3, 4, 6, 8, 10, 12, 16, & 24 hours after dosing. Victrelis: C2: Days 2 & 7; C1: Day 7 pre-dose & 0.5, 1, 2, 3, 4, 6, & 8 hours after AM dose. Up to 72 hours after last dose.

• Safety parameters, including adverse event, concurrent medication, clinical laboratory, ECG, PE, and VS assessments

  Safety will be monitored by PEs, VS, clinical laboratory tests (including blood chemistry, CBC with differential, Troponin I, creatinine phosphokinase, and urinalysis), ECGs, and AE assessments.

  Study Day 1 to 8, and Study Day 14

Study Arms (6)

C 1:INX-08189 50 mg qd X 5 days

EXPERIMENTAL

Cohort 1: Subjects will begin administration of INX-08189 50 mg every day (QD) on Study Day 0. Dosing will occur each morning for 5 days after a fast of at least 8 hours prior to each dose on Study Days 0 through 4. INX-08189 will be administered with water, and subjects will remain fasting for 2 hours following each dose.

Drug: INX-08189 50 mg QD X 5 days

C1: INX-08189 / Victrelis 800 mg TID X 3 days

ACTIVE COMPARATOR

Cohort 1:INX-08189 50 mg QD will be administered concurrently with Victrelis 800 mg three times a day (TID) for 3 additional days

Drug: INX-08189 / Victrelis 800 mg TID X three days

C2: Victrelis 800 mg TID x 3 days

ACTIVE COMPARATOR

Cohort 2: Subjects will begin administration of Victrelis 800 mg three times a day (TID) on the morning of Study Day 0. Victrelis will be administered with water and food with doses at least 7 hours apart. Victrelis 800 mg TID will be administered for a total of 3 days

Drug: Victrelis 800 mg TID x 3 days

C 2:Victrelis 800 mg TID with INX-08189 50 mg QD

ACTIVE COMPARATOR

Cohort 2: Victrelis 800 mg TID will be administered concurrently with INX-08189 50 mg QD for 5 additional days

Drug: Victrelis 800 mg TID with INX-08189 50 mg QD

C1: Placebo with Victrelis 800 mg

PLACEBO COMPARATOR

Cohort 1: Placebo QD will be administered concurrently with Victrelis 800 mg TID for 3 additional days

Drug: Placebo with Victrelis 800 mg

C 2: Victrelis 800 mg with Placebo

PLACEBO COMPARATOR

Cohort 2: Victrelis 800 mg TID will be administered concurrently with Placebo QD for 5 additional days

Drug: Cohort 2: Victrelis 800 mg with Placebo

Interventions

INX-08189 50 mg QD X 5 days DRUG

Cohort 1: Subjects will begin administration of INX-08189 50 mg QD on Study Day 0. Dosing will occur each morning for 5 days after a fast of at least 8 hours prior to each dose on Study Days 0 through 4. INX-08189 will be administered with water, and subjects will remain fasting for 2 hours following each dose.

C 1:INX-08189 50 mg qd X 5 days

INX-08189 / Victrelis 800 mg TID X three days DRUG

Cohort 1: INX-08189 50 mg QD will be administered concurrently with Victrelis 800 mg TID for 3 additional days (Study Days 5 through 7)

C1: INX-08189 / Victrelis 800 mg TID X 3 days

Victrelis 800 mg TID x 3 days DRUG

In Cohort 2, subjects will begin administration of Victrelis 800 mg TID on the morning of Study Day 0. Victrelis will be administered with water and food with doses at least 7 hours apart. Victrelis 800 mg TID will be administered for a total of 3 days (Study Days 0 through 2).

C2: Victrelis 800 mg TID x 3 days

Victrelis 800 mg TID with INX-08189 50 mg QD DRUG

Victrelis 800 mg TID will be administered concurrently with INX-08189 50 mg QD for 5 additional days (Study Days 3 through 7).

C 2:Victrelis 800 mg TID with INX-08189 50 mg QD

Placebo with Victrelis 800 mg DRUG

During combination dosing with INX-08189 and Victrelis, each morning dose will start with INX-08189 or placebo after at least an 8 hour fast, followed by a 2 hour fast with the first Victrelis dose of the day then administered with food.

C1: Placebo with Victrelis 800 mg

Cohort 2: Victrelis 800 mg with Placebo DRUG

During combination dosing with INX-08189 and Victrelis, each morning dose will start with INX-08189 or placebo after at least an 8 hour fast, followed by a 2 hour fast with the first Victrelis dose of the day then administered with food.

C 2: Victrelis 800 mg with Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects must meet the following criteria at the Screening Visit (Visit1), in order to be eligible for study drug administration at Study Day 0 (Visit 3):
• Must be a healthy male or female between 18 and 55 years of age (inclusive) with body mass index (BMI) between 18 and 30 kg/m2 (inclusive), and weigh ≥ 50 kg at the time of signing the informed consent;
• Capable of giving written informed consent that includes compliance with the requirements and restrictions listed in the consent form. Signed informed consent must be on file prior to screening procedures;
• Subject is able to understand and comply with the protocol requirements, instructions and restrictions;
• Must be a non-tobacco user for at least 3 months prior to selection;
• Healthy on the basis of physical examination, medical history, vital signs, electrocardiogram and clinical laboratory tests at screening;
• Women must be postmenopausal for at least 2 years or be surgically sterile with complete hysterectomy or bilateral oophorectomy, and not be pregnant nor breastfeeding;
• Male subjects, who are not surgically sterile with vasectomy, must agree to use a double barrier method of birth control, such as, a condom plus spermicidal agent (foam/gel/film/cream/suppository). This criterion must be followed from the time of the first dose of study medication until 30 days after the last dose of medication. Male subjects cannot donate sperm during the study and for 3 months after receiving the last dose of the study drug.

You may not qualify if:

• Subjects must NOT meet the following criteria at the Screening Visit (Visit1), in order to be eligible for study drug administration at Study Day 0 (Visit 3):
• Infection with Hepatitis A, B or C Virus;
• Infection with the Human Immunodeficiency Virus (HIV);
• History of or any current medical condition which could impact the safety of the participant in the study;
• Current active or underlying gastrointestinal, cardiovascular, neurologic, psychiatric, metabolic, renal, hepatic, respiratory, inflammatory, or infectious disease;
• Clinically significant abnormalities on centrally read ECG;
• Currently significant diarrhea, gastric stasis, or constipation that in the investigator's opinion could influence drug absorption or bioavailability;
• Safety laboratory abnormalities at screening which are clinically significant, or absolute neutrophil count of \< 1800 cells/mm3, or platelet count \< 130,000 cells/mm3, or hemoglobin \< 12 g/dl for women and \< 13 g/dl for men;
• Women of child bearing potential;
• Pregnant or breastfeeding;
• Current abuse of alcohol or illicit drugs, or history of alcohol or illicit drug abuse within the preceding two years;
• A positive urine drug test at screening;
• Consumption of more than 2 units of alcoholic beverages per day or more than 14 units per week (1 unit of alcohol equals 1 glass of beer, 1 glass of wine, 25ml shot of 40% spirit), consumption of alcohol 72 hours before or after study medication intake, consumption of an average of more than five 240 ml servings of coffee or other caffeinated beverages per day;
• Use of chronic prescription medications within 3 months, acute prescription medications within 14 days, or systemic over-the-counter (OTC) medications, including vitamins, within 7 days of starting the study;
• Received an investigational drug or vaccine within 30 days or 5 half lives, whichever is longer, from the receipt of a small molecule or 90 days or 5 half lives, whichever is longer, from the receipt of a large biological molecule prior to Study Day 0, or used an investigational medical device within 30 days prior to Study Day 0, or having participated previously in a study with INX-08189.

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (1)

Prism Research, LLC

Saint Paul, Minnesota, 55114, United States

Location

MeSH Terms

Interventions

BMS-986094; N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide

Study Officials

• Ralph Campaneria, MD

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: FACTORIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2011
• First Posted: November 16, 2011
• Study Start: October 1, 2011
• Primary Completion: November 1, 2011
• Study Completion: November 1, 2011
• Last Updated: June 22, 2012

Record last verified: 2012-06

Locations

US (1)