To Evaluate the Effects of Odalasvir and AL-335 With Simeprevir on the Single-Dose Pharmacokinetics of Ethinylestradiol and Drospirenone in Healthy Female Participants
Phase 1
Completed
- Conditions
- Healthy
- Interventions
- Registration Number
- NCT02885454
- Lead Sponsor
- Janssen Research & Development, LLC
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 24
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
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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)
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Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description OC + AL-335 + ODV + 3-DAA combination Simeprevir (SMV) 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. OC + AL-335 + ODV + 3-DAA combination AL-335 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. OC + AL-335 + ODV + 3-DAA combination Odalasvir (ODV) 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. OC + AL-335 + ODV + 3-DAA combination Drospirenone/ethinylestradiol 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.
- Primary Outcome Measures
Name Time Method Maximum Observed Analyte Concentration (Cmax) of Drospirenone Day 1, 7, 25 and 32: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24, 48 and 72 hours postdose Cmax is the maximum observed analyte concentration.
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC [0-last]) of Drospirenone Day 1, 7, 25 and 32: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24, 48 and 72 hours postdose The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time.
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Drospirenone Day 1, 7, 25 and 32: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24, 48 and 72 hours postdose 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.
Maximum Observed Plasma Concentration (Cmax) of Ethinylestradiol Day 1, 7, 25 and 32: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24, 48 and 72 hours postdose Cmax is the maximum observed analyte concentration.
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC [0-last]) of Ethinylestradiol Day 1, 7, 25 and 32: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24, 48 and 72 hours postdose The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time.
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Ethinylestradiol Day 1, 7, 25 and 32: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24, 48 and 72 hours postdose 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.
- Secondary Outcome Measures
Name Time Method Number of Participants With Adverse Events as a Measure of Safety and Tolerability Approximately 4 Months