To Evaluate the Effects of Odalasvir and AL-335 With Simeprevir on the Single-Dose Pharmacokinetics of Ethinylestradiol and Drospirenone in Healthy Female Participants

A Phase 1, Open-label Study in Healthy Female Subjects to Investigate the Effects of Odalasvir and AL-335 at Steady-state, Given as Single Agents and in Combination With Simeprevir, on the Single-dose Pharmacokinetics of Ethinylestradiol and Drospirenone

The purpose of this study is to evaluate the effect of steady-state concentrations of odalasvir (ODV), AL-335 and the combination of the 3-direct-acting anti-viral agents (3-DAA) ODV, AL-335, and simeprevir (SMV) on the single-dose pharmacokinetic (PK) of drospirenone and ethinylestradiol in healthy female participants.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Drospirenone/ethinylestradiol; Drug: AL-335; Drug: Odalasvir (ODV); Drug: Simeprevir (SMV)

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Overland Park, Kansas, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Participant must be a female of childbearing potential with a normal menstrual cycle
• Participant must have a body mass index (BMI; weight in kg divided by the square of height in meters) between 18.0 and 30.0 kilogram per square meter (kg/m^2), extremes included, and a body weight not less than 50.0 kilogram (kg)
• Participant must have a blood pressure (after the participant is supine for 5 minutes) between 90 and 140 millimeter of mercury (mmHg) systolic, inclusive, and no higher than 90 mmHg diastolic. If blood pressure is out of range, up to 2 repeated assessments are permitted
• Participant must have a negative serum (beta human chorionic gonadotropin [beta- hCG]) pregnancy test at screening
• Participant must have a negative highly sensitive urine pregnancy test at Day -1

Exclusion Criteria:

• Participant is peri- or postmenopausal, or participant with bilateral oophorectomia
• Participant has a history of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) positive, or other clinically active liver disease, or tests positive for HBsAg or anti-HCV at screening
• Participant has previously been dosed with simeprevir (SMV), odalasvir (ODV), or AL-335 in more than 3 single dose studies, or a multiple-dose study with SMV, ODV, or AL-335
• Participant with currently active gynecological disorders including, but not limited to, vaginal bleeding without an obvious reason and hyperprolactinemia with or without galactorrhea
• Participant with a past history of: heart arrhythmias (example, extrasystolic rhythms or tachycardia at rest). Isolated extrasystolic beats are not exclusionary; risk factors associated with Torsade de Pointes such as hypokalemia; family history of short/long QT syndrome; sudden unexplained death (including sudden infant death syndrome [SIDS]) in a first-degree relative (that is, sibling, offspring, or biological parent)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: OC + AL-335 + ODV + 3-DAA combination; Participants will receive single dose of 3 milligram (mg) drospirenone/0.02 mg ethinylestradiol [OC] on Day 1, AL-335 800 mg once daily on Days 5 and 6, a single dose of AL-335 800 mg + a single dose of OC on Day 7, ODV 25 mg once daily on Days 12 to 24, followed by a single dose of ODV 25 mg and a single dose of OC on Day 25, followed by ODV 25 mg + AL-335 800 mg + simeprevir (SMV) 75 mg [3-DAA combination] once daily on Days 26 to 31, followed by a single dose of 3-DAA combination and a single dose of OC on Day 32.

Drug: Drospirenone/ethinylestradiol; Each tablet contains 3 mg drospirenone and 0.02 mg ethinylestradiol to be taken orally on Days 1, 6, 25, and 32.; Other Names: Yaz®; Drug: AL-335; AL-335 (800 mg) tablet once daily on Days 5-7 and then on Days 26-32 (as a component of 3-DAA combination) to be taken orally.; Drug: Odalasvir (ODV); ODV 25 mg tablet once daily on Days 12-25 and then on Days 26-32 (as a component of 3-DAA combination) to be taken orally.; Drug: Simeprevir (SMV); SMV 75 mg capsule as a component of 3-DAA combination to be taken orally on Days 26-32.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Analyte Concentration (Cmax) of Drospirenone	Cmax is the maximum observed analyte concentration.	Day 1, 7, 25 and 32: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24, 48 and 72 hours postdose
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC [0-last]) of Drospirenone	The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time.	Day 1, 7, 25 and 32: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24, 48 and 72 hours postdose
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Drospirenone	The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(0-last) and C(last)/lambda(z); wherein AUC(0-last) is area under the plasma concentration-time curve from time zero to last quantifiable time, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.	Day 1, 7, 25 and 32: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24, 48 and 72 hours postdose
Maximum Observed Plasma Concentration (Cmax) of Ethinylestradiol	Cmax is the maximum observed analyte concentration.	Day 1, 7, 25 and 32: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24, 48 and 72 hours postdose
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC [0-last]) of Ethinylestradiol	The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time.	Day 1, 7, 25 and 32: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24, 48 and 72 hours postdose
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Ethinylestradiol	The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(0-last) and C(last)/lambda(z); wherein AUC(0-last) is area under the plasma concentration-time curve from time zero to last quantifiable time, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.	Day 1, 7, 25 and 32: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24, 48 and 72 hours postdose

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Adverse Events as a Measure of Safety and Tolerability	Approximately 4 Months

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start: August 1, 2016
• Primary Completion (ACTUAL): December 1, 2016
• Study Completion (ACTUAL): December 1, 2016

Study Registration Dates

• First Submitted: August 26, 2016
• First Submitted That Met QC Criteria: August 26, 2016
• First Posted (ESTIMATE): August 31, 2016

Study Record Updates

• Last Update Posted (ESTIMATE): January 23, 2017
• Last Update Submitted That Met QC Criteria: January 20, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Estrogens; Natriuretic Agents; Diuretics; Hormone Antagonists; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Hormonal; Mineralocorticoid Receptor Antagonists; Diuretics, Potassium Sparing; Ethinyl Estradiol; Simeprevir; Drospirenone; Drospirenone and ethinyl estradiol combination; Odalasvir
• Other Study ID Numbers: CR108177; 64294178HPC1001 (OTHER: Janssen Research & Development, LLC)