Study to Evaluate Effect of Sofosbuvir/Velpatasvir/GS-9857 Fixed-Dose Combination on the Pharmacokinetics of a Representative Hormonal Contraceptive Medication, Norgestimate/Ethinyl Estradiol

Phase 1

Completed

• Conditions: HCV Infection
• Interventions: Drug: SOF/VEL/VOX; Drug: VOX; Drug: Norgestimate/ethinyl estradiol

• Registration Number: NCT02533427
• Lead Sponsor: Gilead Sciences

Brief Summary

This study will evaluate the effect of sofosbuvir (SOF)/velpatasvir (VEL)/voxilaprevir (VOX) fixed-dose combination (FDC) + voxilaprevir on the pharmacokinetics (PK) of a representative hormonal contraceptive medication, norgestimate/ethinyl estradiol (Ortho Tri-Cyclen® Lo (OC)) and will assess the effect of norgestimate/ethinyl estradiol on the PK of SOF/VEL/VOX+VOX.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-08-24
• Study First Submitted QC: 2015-08-24
• Study First Posted: 2015-08-26
• Study Start: 2015-10-29
• Primary Completion: 2016-03-18
• Study Completion: 2016-03-18
• Status Verified: 2020-08
• Results First Submitted: 2020-08-17
• Results First Submitted QC: 2020-08-17
• Last Update Submitted: 2020-08-17
• Results First Posted: 2020-09-02
• Last Update Posted: 2020-09-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 15

Inclusion Criteria

• Premenopausal female
• Must have a calculated body mass index (BMI) ≥ 19.0 and ≤ 30.0 kg/m^2 at screening
• Must have a negative serum pregnancy test at screening and urine pregnancy test at Day -1
• Be willing and able to comply with all study requirements.

Exclusion Criteria

• Lactating female

• Have a history of any of the following:

  • Significant drug sensitivity or drug allergy (such as anaphylaxis or hepatoxicity)
  • Known hypersensitivity to the study drugs, the metabolites or formulation excipients

• Believed, by the study investigator, to be inappropriate for study participation for any reason

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
SOF/VEL/VOX + VOX	Norgestimate/ethinyl estradiol	Part A: Participants without a documented history of taking norgestimate/ethinyl estradiol for at least one menstrual cycle will receive norgestimate/ethinyl estradiol. Participants with a documented history of taking norgestimate/ethinyl estradiol may enroll directly into Part B of the study. Part B: Participants will continue taking norgestimate/ethinyl estradiol for the remainder of the study and will receive SOF/VEL/VOX FDC plus VOX.
SOF/VEL/VOX + VOX	VOX	Part A: Participants without a documented history of taking norgestimate/ethinyl estradiol for at least one menstrual cycle will receive norgestimate/ethinyl estradiol. Participants with a documented history of taking norgestimate/ethinyl estradiol may enroll directly into Part B of the study. Part B: Participants will continue taking norgestimate/ethinyl estradiol for the remainder of the study and will receive SOF/VEL/VOX FDC plus VOX.
SOF/VEL/VOX + VOX	SOF/VEL/VOX	Part A: Participants without a documented history of taking norgestimate/ethinyl estradiol for at least one menstrual cycle will receive norgestimate/ethinyl estradiol. Participants with a documented history of taking norgestimate/ethinyl estradiol may enroll directly into Part B of the study. Part B: Participants will continue taking norgestimate/ethinyl estradiol for the remainder of the study and will receive SOF/VEL/VOX FDC plus VOX.

Primary Outcome Measures

Name	Time	Method
PK Parameter: AUCtau of Norgestrel	Cycle 1,Study Day 14: Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours postdose; Cycle 2,Study Day 42: Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours postdose	AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
PK Parameter: AUCtau of Ethinyl Estradiol	Cycle 1,Study Day 14: Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours postdose; Cycle 2,Study Day 42: Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours postdose	AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
Pharmacokinetic (PK) Parameter: AUCtau of Norgestimate	Cycle 1,Study Day 14:Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours postdose; Cycle 2,Study Day 42: Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours postdose	AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
Pharmacokinetic (PK) Parameter: AUCtau of Norelgestromin	Cycle 1,Study Day 14: Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours postdose; Cycle 2,Study Day 42: Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours postdose	AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
PK Parameter: Cmax of Ethinyl Estradiol	Cycle 1,Study Day 14: Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours postdose; Cycle 2,Study Day 42: Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours postdose	Cmax is defined as the maximum concentration of drug.
PK Parameter: Ctau of Ethinyl Estradiol	Cycle 1,Study Day 14: Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours postdose; Cycle 2,Study Day 42: Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours postdose	Ctau is defined as the observed drug concentration at the end of the dosing interval.
PK Parameter: Cmax of Norelgestromin	Cycle 1,Study Day 14:Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours postdose; Cycle 2,Study Day 42: Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours postdose	Cmax is defined as the maximum concentration of drug.
PK Parameter: Cmax of Norgestrel	Cycle 1,Study Day 14: Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours postdose; Cycle 2,Study Day 42: Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours postdose	Cmax is defined as the maximum concentration of drug.
PK Parameter: Ctau of Norgestrel	Cycle 1,Study Day 14: Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours postdose; Cycle 2,Study Day 42: Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours postdose	Ctau is defined as the observed drug concentration at the end of the dosing interval.
PK Parameter: Cmax of Norgestimate	Cycle 1,Study Day 14: Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours postdose; Cycle 2,Study Day 42: Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours postdose	Cmax is defined as the maximum concentration of drug.
PK Parameter: Ctau of Norelgestromin	Part A:Cycle 1,Study Day 14:Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours postdose; Part B:Cycle 2,Study Day 42:Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours postdose	Ctau is defined as the observed drug concentration at the end of the dosing interval.
PK Parameter: Ctau of Norgestimate	Cycle 1,Study Day 14: Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours postdose;Cycle 2,Study Day 42: Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours postdose	Ctau is defined as the observed drug concentration at the end of the dosing interval.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Who Experienced Treatment-Emergent Adverse Events	First dose date up to the last dose date (maximum: 84 days) plus 10 days
Percentage of Participants Who Experienced Laboratory Abnormalities	First dose date up to the last dose date (maximum: 84 days) plus 10 days	Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. The most severe graded abnormality from all tests was counted for each participant. Grade 1: mild; Grade 2: moderate;Grade 3: severe or medically significant but not immediately life-threatening; Grade 4: life-threatening consequences.
PK Parameter: Tmax of Norelgestromin, Norgestrel, Ethinyl Estradiol, and Norgestimate	Cycle 1,Study Day 14: Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours postdose; Cycle 2,Study Day 42: Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours postdose	Tmax is defined as the time (observed time point) of Cmax.
PK Parameter: λz of Norelgestromin, Norgestrel, Ethinyl Estradiol, and Norgestimate	Cycle 1,Study Day 14: Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours postdose; Cycle 2,Study Day 42:Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours postdose	λz is defined as the terminal elimination rate constant, estimated by linear regression of the terminal elimination phase of the log plasma concentration of drug versus time curve of the drug.
PK Parameter: λz of SOF, SOF Metabolites (GS-566500 and GS-331007), VEL, and VOX	Cycle 2, Study Day 42: Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours postdose	λz is defined as the terminal elimination rate constant, estimated by linear regression of the terminal elimination phase of the log plasma concentration of drug versus time curve of the drug.
PK Parameter: CLss/F Ethinyl Estradiol, and Norgestimate	\Cycle 1,Study Day 14: Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours postdose; Cycle 2,Study Day 42: Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours postdose	CLss/F is defined as the apparent steady state oral clearance following administration of the drug.
PK Parameter: Cmax of Sofosbuvir (SOF), SOF Metabolites (GS-566500 and GS-331007), Velpatasvir (VEL), and Voxilaprevir (VOX)	Cycle 2, Study Day 42: Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours postdose	Cmax is defined as the maximum concentration of drug.
PK Parameter: Tlast of SOF, SOF Metabolites (GS-566500 and GS-331007), VEL, and VOX	Cycle 2, Study Day 42: Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours postdose	Tlast is defined as the time (observed time point) of Clast.
PK Parameter: AUCtau of SOF, SOF Metabolites (GS-566500 and GS-331007), VEL, and VOX	Cycle 2, Study Day 42: Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours postdose	AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
PK Parameter: CLss/F of SOF, VEL, and VOX	Cycle 2, Study Day 42: Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours postdose	CLss/F is defined as the apparent steady state oral clearance following administration of the drug.
PK Parameter: Tlast of Norelgestromin, Norgestrel, Ethinyl Estradiol, and Norgestimate	Cycle 1,Study Day 14: Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours postdose; Cycle 2,Study Day 42: Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours postdose	Tlast is defined as the time (observed time point) of Clast.
PK Parameter: t1/2 of Norelgestromin, Norgestrel, Ethinyl Estradiol, and Norgestimate	Cycle 1,Study Day 14: Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours postdose; Cycle 2,Study Day 42: Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours postdose	t1/2 is defined as the estimate of the terminal elimination half-life of the drug.
PK Parameter: Tmax of SOF, SOF Metabolites (GS-566500 and GS-331007), VEL, and VOX	Cycle 2, Study Day 42: Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours postdose	Tmax is defined as the time (observed time point) of Cmax.
PK Parameter: Ctau of SOF Metabolites (GS-566500 and GS-331007), VEL, and VOX	Cycle 2, Study Day 42: Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours postdose	Ctau is defined as the observed drug concentration at the end of the dosing interval.
PK Parameter: t1/2 of SOF, SOF Metabolites (GS-566500 and GS-331007), VEL, and VOX	Cycle 2, Study Day 42: Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours postdose	t1/2 is defined as the estimate of the terminal elimination half-life of the drug.