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

Sponsor
Gilead Sciences (Industry)
Overall Status
Completed
CT.gov ID
NCT02533427
Collaborator
(none)
15
1
1
4.6
3.2

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
15 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1, Open-Label, Drug Interaction Study Evaluating the Effect of Sofosbuvir/Velpatasvir/GS-9857 Fixed-Dose Combination on the Pharmacokinetics of a Representative Hormonal Contraceptive Medication, Norgestimate/Ethinyl Estradiol
Actual Study Start Date :
Oct 29, 2015
Actual Primary Completion Date :
Mar 18, 2016
Actual Study Completion Date :
Mar 18, 2016

Arms and Interventions

Arm Intervention/Treatment
Experimental: SOF/VEL/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.

Drug: SOF/VEL/VOX
400/100/100 mg FDC tablet administered orally once daily
Other Names:
  • Epclusa®
  • Drug: VOX
    100 mg tablet administered orally once daily
    Other Names:
  • GS-9857
  • Drug: Norgestimate/ethinyl estradiol
    Norgestimate 0.180 mg/0.215 mg/0.25 mg/ethinyl estradiol 0.025 mg tablet administered orally once daily according to the package insert
    Other Names:
  • Ortho-Tri-Cyclen® Lo
  • Outcome Measures

    Primary Outcome Measures

    1. 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).

    2. 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).

    3. 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).

    4. 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).

    5. 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.

    6. 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.

    7. 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.

    8. 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.

    9. 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.

    10. 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.

    11. 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.

    12. 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

    1. Percentage of Participants Who Experienced Treatment-Emergent Adverse Events [First dose date up to the last dose date (maximum: 84 days) plus 10 days]

    2. 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.

    3. 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.

    4. 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.

    5. 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.

    6. 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.

    7. 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.

    8. 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.

    9. 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.

    10. 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.

    11. 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.

    12. 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.

    13. 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).

    14. 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.

    15. 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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 45 Years
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    Yes
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Christchurch New Zealand

    Sponsors and Collaborators

    • Gilead Sciences

    Investigators

    • Study Director: Gilead Study Director, Gilead Sciences

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Gilead Sciences
    ClinicalTrials.gov Identifier:
    NCT02533427
    Other Study ID Numbers:
    • GS-US-367-1909
    First Posted:
    Aug 26, 2015
    Last Update Posted:
    Sep 2, 2020
    Last Verified:
    Aug 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details Participants were enrolled at a study site in New Zealand. The first participant was screened on 29 October 2015. The last study visit occurred on 18 March 2016.
    Pre-assignment Detail 15 participants were screened.
    Arm/Group Title NGM/EE + SOF/VEL/VOX + VOX (Part A and Part B)
    Arm/Group Description Part A: Participants without a documented history of taking norgestimate/ethinyl estradiol (NGM/EE) for at least one menstrual cycle received NGM 0.180 mg/0.215 mg/0.25 mg/ EE 0.025 mg tablet orally once daily for one cycle (cycle=28 days). Part B: Participants continued NGM/EE through Cycle 1 and 2 received sofosbuvir (SOF)/velpatasvir (VEL)/voxilaprevir (VOX) fixed dose combination (FDC) 400/100/100 mg tablet + VOX 100 mg tablet orally once daily during cycle 2 (cycle=28 days).
    Period Title: Overall Study
    STARTED 15
    COMPLETED 15
    NOT COMPLETED 0

    Baseline Characteristics

    Arm/Group Title NGM/EE + SOF/VEL/VOX + VOX (Part A and Part B)
    Arm/Group Description Part A: Participants without a documented history of taking norgestimate/ethinyl estradiol (NGM/EE) for at least one menstrual cycle received NGM 0.180 mg/0.215 mg/0.25 mg/ EE 0.025 mg tablet orally once daily for one cycle (cycle=28 days). Part B: Participants continued NGM/EE through Cycle 1 and 2 received sofosbuvir (SOF)/velpatasvir (VEL)/voxilaprevir (VOX) fixed dose combination (FDC) 400/100/100 mg tablet + VOX 100 mg tablet orally once daily during cycle 2 (cycle=28 days).
    Overall Participants 15
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    24
    (4.8)
    Sex: Female, Male (Count of Participants)
    Female
    15
    100%
    Male
    0
    0%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    Not Hispanic or Latino
    15
    100%
    Unknown or Not Reported
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    Asian
    0
    0%
    Native Hawaiian or Other Pacific Islander
    1
    6.7%
    Black or African American
    0
    0%
    White
    14
    93.3%
    More than one race
    0
    0%
    Unknown or Not Reported
    0
    0%

    Outcome Measures

    1. Primary Outcome
    Title Pharmacokinetic (PK) Parameter: AUCtau of Norelgestromin
    Description AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    The PK Analysis Set included all enrolled participants who took at least 1 dose of study drug and had at least 1 non-missing postdose plasma concentration value reported.
    Arm/Group Title Part A: NGM/EE Part B: NGM/EE + SOF/VEL/VOX + VOX
    Arm/Group Description Participants received NGM 0.180 mg/0.215 mg/0.25 mg/ EE 0.025 mg tablet orally once daily for cycle 1 (cycle = 28 days). Participants received NGM 0.180 mg/0.215 mg/0.25 mg/ EE 0.025 mg + sofosbuvir (SOF)/velpatasvir (VEL)/voxilaprevir (VOX) FDC 400/100/100 mg tablet + VOX 100 mg tablet orally once daily during cycle 2 (cycle = 28 days).
    Measure Participants 15 15
    Mean (Standard Deviation) [hours*picogram/milliliter (h*pg/mL)]
    13757.4
    (2478.44)
    14690.4
    (2116.43)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Part A: NGM/EE, Part B: NGM/EE + SOF/VEL/VOX + VOX
    Comments Norelgestromin Part B/Part A
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter % Geometric Least Square Mean(GLSM)Ratio
    Estimated Value 107.36
    Confidence Interval (2-Sided) 90%
    103.19 to 111.69
    Parameter Dispersion Type:
    Value:
    Estimation Comments Test/Reference: Norelgestromin Part B/Part A
    2. Primary Outcome
    Title PK Parameter: AUCtau of Norgestrel
    Description AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    Participants in the PK Analysis Set were analyzed.
    Arm/Group Title Part A: NGM/EE Part B: NGM/EE + SOF/VEL/VOX + VOX
    Arm/Group Description Participants received NGM 0.180 mg/0.215 mg/0.25 mg/ EE 0.025 mg tablet orally once daily for cycle 1 (cycle = 28 days). Participants received NGM 0.180 mg/0.215 mg/0.25 mg/ EE 0.025 mg + sofosbuvir (SOF)/velpatasvir (VEL)/voxilaprevir (VOX) FDC 400/100/100 mg tablet + VOX 100 mg tablet orally once daily during cycle 2 (cycle = 28 days).
    Measure Participants 15 15
    Mean (Standard Deviation) [hours*nanogram/milliliter (h*ng/mL)]
    41.1
    (11.05)
    47.3
    (13.19)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Part A: NGM/EE, Part B: NGM/EE + SOF/VEL/VOX + VOX
    Comments Norgestrel Part B/Part A
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter % GLSM Ratio
    Estimated Value 115.14
    Confidence Interval (2-Sided) 90%
    106.49 to 124.50
    Parameter Dispersion Type:
    Value:
    Estimation Comments Test/Reference: Norgestrel Part B/Part A
    3. Primary Outcome
    Title PK Parameter: AUCtau of Ethinyl Estradiol
    Description AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    Participants in the PK Analysis Set were analyzed.
    Arm/Group Title Part A: NGM/EE Part B: NGM/EE + SOF/VEL/VOX + VOX
    Arm/Group Description Participants received NGM 0.180 mg/0.215 mg/0.25 mg/ EE 0.025 mg tablet orally once daily for cycle 1 (cycle = 28 days). Participants received NGM 0.180 mg/0.215 mg/0.25 mg/ EE 0.025 mg + sofosbuvir (SOF)/velpatasvir (VEL)/voxilaprevir (VOX) FDC 400/100/100 mg tablet + VOX 100 mg tablet orally once daily during cycle 2 (cycle = 28 days).
    Measure Participants 15 15
    Mean (Standard Deviation) [h*pg/mL]
    835.2
    (367.17)
    871.4
    (355.33)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Part A: NGM/EE, Part B: NGM/EE + SOF/VEL/VOX + VOX
    Comments Ethinyl estradiol Part B/Part A
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter % GLSM Ratio
    Estimated Value 105.43
    Confidence Interval (2-Sided) 90%
    96.95 to 114.66
    Parameter Dispersion Type:
    Value:
    Estimation Comments Test/Reference: Ethinyl estradiol Part B/Part A
    4. Primary Outcome
    Title Pharmacokinetic (PK) Parameter: AUCtau of Norgestimate
    Description AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    Participants in the PK Analysis Set with available data were analyzed.
    Arm/Group Title Part A: NGM/EE Part B: NGM/EE + SOF/VEL/VOX + VOX
    Arm/Group Description Participants received NGM 0.180 mg/0.215 mg/0.25 mg/ EE 0.025 mg tablet orally once daily for cycle 1 (cycle = 28 days). Participants received NGM 0.180 mg/0.215 mg/0.25 mg/ EE 0.025 mg + sofosbuvir (SOF)/velpatasvir (VEL)/voxilaprevir (VOX) FDC 400/100/100 mg tablet + VOX 100 mg tablet orally once daily during cycle 2 (cycle = 28 days).
    Measure Participants 1 4
    Mean (Standard Deviation) [h*ng/mL]
    0.2
    (NA)
    0.5
    (0.48)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Part A: NGM/EE, Part B: NGM/EE + SOF/VEL/VOX + VOX
    Comments Norgestimate Part B/Part A
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter % GLSM Ratio
    Estimated Value 248.89
    Confidence Interval (2-Sided) 90%
    33.11 to 1870.81
    Parameter Dispersion Type:
    Value:
    Estimation Comments Test/Reference: Norgestimate Part B/Part A
    5. Primary Outcome
    Title PK Parameter: Cmax of Norelgestromin
    Description Cmax is defined as the maximum concentration of drug.
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    Participants in the PK Analysis Set were analyzed.
    Arm/Group Title Part A: NGM/EE Part B: NGM/EE + SOF/VEL/VOX + VOX
    Arm/Group Description Participants received NGM 0.180 mg/0.215 mg/0.25 mg/ EE 0.025 mg tablet orally once daily for cycle 1 (cycle = 28 days). Participants received NGM 0.180 mg/0.215 mg/0.25 mg/ EE 0.025 mg + sofosbuvir (SOF)/velpatasvir (VEL)/voxilaprevir (VOX) FDC 400/100/100 mg tablet + VOX 100 mg tablet orally once daily during cycle 2 (cycle = 28 days).
    Measure Participants 15 15
    Mean (Standard Deviation) [pg/mL]
    1080.9
    (221.11)
    1162.2
    (209.53)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Part A: NGM/EE, Part B: NGM/EE + SOF/VEL/VOX + VOX
    Comments Norelgestromin Part B/Part A
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter % GLSM Ratio
    Estimated Value 107.71
    Confidence Interval (2-Sided) 90%
    97.78 to 118.65
    Parameter Dispersion Type:
    Value:
    Estimation Comments Test/Reference: Norelgestromin Part B/Part A
    6. Primary Outcome
    Title PK Parameter: Cmax of Norgestrel
    Description Cmax is defined as the maximum concentration of drug.
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    Participants in the PK Analysis Set were analyzed.
    Arm/Group Title Part A: NGM/EE Part B: NGM/EE + SOF/VEL/VOX + VOX
    Arm/Group Description Participants received NGM 0.180 mg/0.215 mg/0.25 mg/ EE 0.025 mg tablet orally once daily for cycle 1 (cycle = 28 days). Participants received NGM 0.180 mg/0.215 mg/0.25 mg/ EE 0.025 mg + sofosbuvir (SOF)/velpatasvir (VEL)/voxilaprevir (VOX) FDC 400/100/100 mg tablet + VOX 100 mg tablet orally once daily during cycle 2 (cycle = 28 days).
    Measure Participants 15 15
    Mean (Standard Deviation) [ng/mL]
    2.0
    (0.52)
    2.3
    (0.61)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Part A: NGM/EE, Part B: NGM/EE + SOF/VEL/VOX + VOX
    Comments Norgestrel Part B/Part A
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter % GLSM Ratio
    Estimated Value 115.02
    Confidence Interval (2-Sided) 90%
    108.12 to 122.37
    Parameter Dispersion Type:
    Value:
    Estimation Comments Test/Reference: Norgestrel Part B/Part A
    7. Primary Outcome
    Title PK Parameter: Cmax of Ethinyl Estradiol
    Description Cmax is defined as the maximum concentration of drug.
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    Participants in the PK Analysis Set were analyzed.
    Arm/Group Title Part A: NGM/EE Part B: NGM/EE + SOF/VEL/VOX + VOX
    Arm/Group Description Participants received NGM 0.180 mg/0.215 mg/0.25 mg/ EE 0.025 mg tablet orally once daily for cycle 1 (cycle = 28 days). Participants received NGM 0.180 mg/0.215 mg/0.25 mg/ EE 0.025 mg + sofosbuvir (SOF)/velpatasvir (VEL)/voxilaprevir (VOX) FDC 400/100/100 mg tablet + VOX 100 mg tablet orally once daily during cycle 2 (cycle = 28 days).
    Measure Participants 15 15
    Mean (Standard Deviation) [pg/mL]
    68.4
    (31.06)
    80.6
    (28.44)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Part A: NGM/EE, Part B: NGM/EE + SOF/VEL/VOX + VOX
    Comments Ethinyl estradiol Part B/Part A
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter % GLSM Ratio
    Estimated Value 121.06
    Confidence Interval (2-Sided) 90%
    106.10 to 138.12
    Parameter Dispersion Type:
    Value:
    Estimation Comments Test/Reference: Ethinyl estradiol Part B/Part A
    8. Primary Outcome
    Title PK Parameter: Cmax of Norgestimate
    Description Cmax is defined as the maximum concentration of drug.
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    Participants in the PK Analysis Set were analyzed.
    Arm/Group Title Part A: NGM/EE Part B: NGM/EE + SOF/VEL/VOX + VOX
    Arm/Group Description Participants received NGM 0.180 mg/0.215 mg/0.25 mg/ EE 0.025 mg tablet orally once daily for cycle 1 (cycle = 28 days). Participants received NGM 0.180 mg/0.215 mg/0.25 mg/ EE 0.025 mg + sofosbuvir (SOF)/velpatasvir (VEL)/voxilaprevir (VOX) FDC 400/100/100 mg tablet + VOX 100 mg tablet orally once daily during cycle 2 (cycle = 28 days).
    Measure Participants 15 15
    Mean (Standard Deviation) [ng/mL]
    0.0
    (0.04)
    0.1
    (0.05)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Part A: NGM/EE, Part B: NGM/EE + SOF/VEL/VOX + VOX
    Comments Norgestimate Part B/Part A
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter % GLSM Ratio
    Estimated Value 112.11
    Confidence Interval (2-Sided) 90%
    87.19 to 144.14
    Parameter Dispersion Type:
    Value:
    Estimation Comments Test/Reference: Norgestimate Part B/Part A
    9. Primary Outcome
    Title PK Parameter: Ctau of Norelgestromin
    Description Ctau is defined as the observed drug concentration at the end of the dosing interval.
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    Participants in the PK Analysis Set were analyzed.
    Arm/Group Title Part A: NGM/EE Part B: NGM/EE + SOF/VEL/VOX + VOX
    Arm/Group Description Participants received NGM 0.180 mg/0.215 mg/0.25 mg/ EE 0.025 mg tablet orally once daily for cycle 1 (cycle = 28 days). Participants received NGM 0.180 mg/0.215 mg/0.25 mg/ EE 0.025 mg + sofosbuvir (SOF)/velpatasvir (VEL)/voxilaprevir (VOX) FDC 400/100/100 mg tablet + VOX 100 mg tablet orally once daily during cycle 2 (cycle = 28 days).
    Measure Participants 15 15
    Mean (Standard Deviation) [picogram/milliliter (pg/mL)]
    364.1
    (76.74)
    413.9
    (73.78)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Part A: NGM/EE, Part B: NGM/EE + SOF/VEL/VOX + VOX
    Comments Norelgestromin Part B/Part A
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter % GLSM Ratio
    Estimated Value 114.19
    Confidence Interval (2-Sided) 90%
    107.40 to 121.39
    Parameter Dispersion Type:
    Value:
    Estimation Comments Test/Reference: Norelgestromin Part B/Part A
    10. Primary Outcome
    Title PK Parameter: Ctau of Norgestrel
    Description Ctau is defined as the observed drug concentration at the end of the dosing interval.
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    Participants in the PK Analysis Set were analyzed.
    Arm/Group Title Part A: NGM/EE Part B: NGM/EE + SOF/VEL/VOX + VOX
    Arm/Group Description Participants received NGM 0.180 mg/0.215 mg/0.25 mg/ EE 0.025 mg tablet orally once daily for cycle 1 (cycle = 28 days). Participants received NGM 0.180 mg/0.215 mg/0.25 mg/ EE 0.025 mg + sofosbuvir (SOF)/velpatasvir (VEL)/voxilaprevir (VOX) FDC 400/100/100 mg tablet + VOX 100 mg tablet orally once daily during cycle 2 (cycle = 28 days).
    Measure Participants 15 15
    Mean (Standard Deviation) [nanogram/milliliter (ng/mL)]
    1.5
    (0.37)
    1.8
    (0.55)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Part A: NGM/EE, Part B: NGM/EE + SOF/VEL/VOX + VOX
    Comments Norgestrel Part B/Part A
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter % GLSM Ratio
    Estimated Value 121.62
    Confidence Interval (2-Sided) 90%
    110.85 to 133.44
    Parameter Dispersion Type:
    Value:
    Estimation Comments Test/Reference: Norgestrel Part B/Part A
    11. Primary Outcome
    Title PK Parameter: Ctau of Ethinyl Estradiol
    Description Ctau is defined as the observed drug concentration at the end of the dosing interval.
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    Participants in the PK Analysis Set were analyzed.
    Arm/Group Title Part A: NGM/EE Part B: NGM/EE + SOF/VEL/VOX + VOX
    Arm/Group Description Participants received NGM 0.180 mg/0.215 mg/0.25 mg/ EE 0.025 mg tablet orally once daily for cycle 1 (cycle = 28 days). Participants received NGM 0.180 mg/0.215 mg/0.25 mg/ EE 0.025 mg + sofosbuvir (SOF)/velpatasvir (VEL)/voxilaprevir (VOX) FDC 400/100/100 mg tablet + VOX 100 mg tablet orally once daily during cycle 2 (cycle = 28 days).
    Measure Participants 15 15
    Mean (Standard Deviation) [pg/mL]
    19.7
    (10.82)
    18.2
    (10.39)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Part A: NGM/EE, Part B: NGM/EE + SOF/VEL/VOX + VOX
    Comments Ethinyl estradiol Part B/Part A
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter % GLSM Ratio
    Estimated Value 92.86
    Confidence Interval (2-Sided) 90%
    82.55 to 104.45
    Parameter Dispersion Type:
    Value:
    Estimation Comments Test/Reference: Ethinyl estradiol Part B/Part A
    12. Primary Outcome
    Title PK Parameter: Ctau of Norgestimate
    Description Ctau is defined as the observed drug concentration at the end of the dosing interval.
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    Participants in the PK Analysis Set with available data were analyzed.
    Arm/Group Title Part A: NGM/EE Part B: NGM/EE + SOF/VEL/VOX + VOX
    Arm/Group Description Participants received NGM 0.180 mg/0.215 mg/0.25 mg/ EE 0.025 mg tablet orally once daily for cycle 1 (cycle = 28 days). Participants received NGM 0.180 mg/0.215 mg/0.25 mg/ EE 0.025 mg + sofosbuvir (SOF)/velpatasvir (VEL)/voxilaprevir (VOX) FDC 400/100/100 mg tablet + VOX 100 mg tablet orally once daily during cycle 2 (cycle = 28 days).
    Measure Participants 6 3
    Mean (Standard Deviation) [ng/mL]
    0.0
    (0.00)
    0.0
    (0.00)
    13. Secondary Outcome
    Title Percentage of Participants Who Experienced Treatment-Emergent Adverse Events
    Description
    Time Frame First dose date up to the last dose date (maximum: 84 days) plus 10 days

    Outcome Measure Data

    Analysis Population Description
    The Safety Analysis Set included all enrolled participants who took at least 1 dose of study drug.
    Arm/Group Title Part A: NGM/EE Part B: NGM/EE + SOF/VEL/VOX + VOX
    Arm/Group Description Participants received NGM 0.180 mg/0.215 mg/0.25 mg/ EE 0.025 mg tablet orally once daily for cycle 1 (cycle = 28 days). Participants received NGM 0.180 mg/0.215 mg/0.25 mg/ EE 0.025 mg + sofosbuvir (SOF)/velpatasvir (VEL)/voxilaprevir (VOX) FDC 400/100/100 mg tablet + VOX 100 mg tablet orally once daily during cycle 2 (cycle = 28 days).
    Measure Participants 15 15
    Number [percentage of participants]
    66.7
    444.7%
    93.3
    NaN
    14. Secondary Outcome
    Title Percentage of Participants Who Experienced Laboratory Abnormalities
    Description 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.
    Time Frame First dose date up to the last dose date (maximum: 84 days) plus 10 days

    Outcome Measure Data

    Analysis Population Description
    Participants in the Safety Analysis Set were analyzed.
    Arm/Group Title Part A: NGM/EE Part B: NGM/EE + SOF/VEL/VOX + VOX
    Arm/Group Description Participants received NGM 0.180 mg/0.215 mg/0.25 mg/ EE 0.025 mg tablet orally once daily for cycle 1 (cycle = 28 days). Participants received NGM 0.180 mg/0.215 mg/0.25 mg/ EE 0.025 mg + sofosbuvir (SOF)/velpatasvir (VEL)/voxilaprevir (VOX) FDC 400/100/100 mg tablet + VOX 100 mg tablet orally once daily during cycle 2 (cycle = 28 days).
    Measure Participants 15 15
    Grade 1
    60.0
    400%
    53.3
    NaN
    Grade 2
    13.3
    88.7%
    6.7
    NaN
    Grade 3
    13.3
    88.7%
    0.0
    NaN
    Grade 4
    0.0
    0%
    0.0
    NaN
    15. Secondary Outcome
    Title PK Parameter: Tmax of Norelgestromin, Norgestrel, Ethinyl Estradiol, and Norgestimate
    Description Tmax is defined as the time (observed time point) of Cmax.
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    Participants in the PK Analysis Set with available were analyzed.
    Arm/Group Title Part A: NGM/EE Part B: NGM/EE + SOF/VEL/VOX + VOX
    Arm/Group Description Participants received NGM 0.180 mg/0.215 mg/0.25 mg/ EE 0.025 mg tablet orally once daily for cycle 1 (cycle = 28 days). Participants received NGM 0.180 mg/0.215 mg/0.25 mg/ EE 0.025 mg + sofosbuvir (SOF)/velpatasvir (VEL)/voxilaprevir (VOX) FDC 400/100/100 mg tablet + VOX 100 mg tablet orally once daily during cycle 2 (cycle = 28 days).
    Measure Participants 15 15
    Norelgestromin
    3.00
    3.00
    Norgestrel
    4.00
    4.00
    Ethinyl Estradiol
    3.00
    2.00
    Norgestimate
    1.50
    1.50
    16. Secondary Outcome
    Title PK Parameter: Tlast of Norelgestromin, Norgestrel, Ethinyl Estradiol, and Norgestimate
    Description Tlast is defined as the time (observed time point) of Clast.
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    Participants in the PK Analysis Set with available data were analyzed.
    Arm/Group Title Part A: NGM/EE Part B: NGM/EE + SOF/VEL/VOX + VOX
    Arm/Group Description Participants received NGM 0.180 mg/0.215 mg/0.25 mg/ EE 0.025 mg tablet orally once daily for cycle 1 (cycle = 28 days). Participants received NGM 0.180 mg/0.215 mg/0.25 mg/ EE 0.025 mg + sofosbuvir (SOF)/velpatasvir (VEL)/voxilaprevir (VOX) FDC 400/100/100 mg tablet + VOX 100 mg tablet orally once daily during cycle 2 (cycle = 28 days).
    Measure Participants 15 15
    Norelgestromin
    24.00
    24.00
    Norgestrel
    24.00
    24.00
    Ethinyl Estradiol
    24.00
    24.00
    Norgestimate
    1.50
    2.75
    17. Secondary Outcome
    Title PK Parameter: λz of Norelgestromin, Norgestrel, Ethinyl Estradiol, and Norgestimate
    Description 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.
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    Participants in the PK Analysis Set with available data were analyzed.
    Arm/Group Title Part A: NGM/EE Part B: NGM/EE + SOF/VEL/VOX + VOX
    Arm/Group Description Participants received NGM 0.180 mg/0.215 mg/0.25 mg/ EE 0.025 mg tablet orally once daily for cycle 1 (cycle = 28 days). Participants received NGM 0.180 mg/0.215 mg/0.25 mg/ EE 0.025 mg + sofosbuvir (SOF)/velpatasvir (VEL)/voxilaprevir (VOX) FDC 400/100/100 mg tablet + VOX 100 mg tablet orally once daily during cycle 2 (cycle = 28 days).
    Measure Participants 15 15
    Norelgestromin
    0.035
    (0.0095)
    0.025
    (0.0084)
    Norgestrel
    0.016
    (0.0081)
    0.012
    (0.0039)
    Ethinyl Estradiol
    0.053
    (0.0230)
    0.059
    (0.0186)
    Norgestimate
    0.674
    (NA)
    0.392
    (0.3674)
    18. Secondary Outcome
    Title PK Parameter: t1/2 of Norelgestromin, Norgestrel, Ethinyl Estradiol, and Norgestimate
    Description t1/2 is defined as the estimate of the terminal elimination half-life of the drug.
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    Participants in the PK Analysis Set with available data were analyzed.
    Arm/Group Title Part A: NGM/EE Part B: NGM/EE + SOF/VEL/VOX + VOX
    Arm/Group Description Participants received NGM 0.180 mg/0.215 mg/0.25 mg/ EE 0.025 mg tablet orally once daily for cycle 1 (cycle = 28 days). Participants received NGM 0.180 mg/0.215 mg/0.25 mg/ EE 0.025 mg + sofosbuvir (SOF)/velpatasvir (VEL)/voxilaprevir (VOX) FDC 400/100/100 mg tablet + VOX 100 mg tablet orally once daily during cycle 2 (cycle = 28 days).
    Measure Participants 15 15
    Norelgestromin
    18.91
    28.95
    Norgestrel
    33.76
    57.42
    Ethinyl Estradiol
    13.68
    10.78
    Norgestimate
    1.03
    2.30
    19. Secondary Outcome
    Title PK Parameter: CLss/F Ethinyl Estradiol, and Norgestimate
    Description CLss/F is defined as the apparent steady state oral clearance following administration of the drug.
    Time Frame \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

    Outcome Measure Data

    Analysis Population Description
    Participants in the PK Analysis Set with available data were analyzed.
    Arm/Group Title Part A: NGM/EE Part B: NGM/EE + SOF/VEL/VOX + VOX
    Arm/Group Description Participants received NGM 0.180 mg/0.215 mg/0.25 mg/ EE 0.025 mg tablet orally once daily for cycle 1 (cycle = 28 days). Participants received NGM 0.180 mg/0.215 mg/0.25 mg/ EE 0.025 mg + sofosbuvir (SOF)/velpatasvir (VEL)/voxilaprevir (VOX) FDC 400/100/100 mg tablet + VOX 100 mg tablet orally once daily during cycle 2 (cycle = 28 days).
    Measure Participants 15 15
    Ethinyl Estradiol
    34226.8
    (12691.91)
    32000.0
    (9530.52)
    Norgestimate
    1285855.5
    (NA)
    617498.8
    (350620.05)
    20. Secondary Outcome
    Title PK Parameter: Cmax of Sofosbuvir (SOF), SOF Metabolites (GS-566500 and GS-331007), Velpatasvir (VEL), and Voxilaprevir (VOX)
    Description Cmax is defined as the maximum concentration of drug.
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    Participants in the PK Analysis Set who were enrolled in Part B and received NGM+ SOV/VEL/VOX + VOX were analyzed.
    Arm/Group Title Part B: NGM/EE + SOF/VEL/VOX + VOX
    Arm/Group Description Participants received NGM 0.180 mg/0.215 mg/0.25 mg/ EE 0.025 mg + sofosbuvir (SOF)/velpatasvir (VEL)/voxilaprevir (VOX) FDC 400/100/100 mg tablet + VOX 100 mg tablet orally once daily during cycle 2 (cycle = 28 days).
    Measure Participants 15
    SOF
    967.6
    (322.20)
    GS-566500
    491.1
    (107.66)
    GS-331007
    979.4
    (119.43)
    VEL
    853.3
    (161.60)
    VOX
    512.4
    (171.71)
    21. Secondary Outcome
    Title PK Parameter: Tmax of SOF, SOF Metabolites (GS-566500 and GS-331007), VEL, and VOX
    Description Tmax is defined as the time (observed time point) of Cmax.
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    Participants in the PK Analysis Set who were enrolled in Part B and received NGM+ SOV/VEL/VOX + VOX were analyzed.
    Arm/Group Title Part B: NGM/EE + SOF/VEL/VOX + VOX
    Arm/Group Description Participants received NGM 0.180 mg/0.215 mg/0.25 mg/ EE 0.025 mg + sofosbuvir (SOF)/velpatasvir (VEL)/voxilaprevir (VOX) FDC 400/100/100 mg tablet + VOX 100 mg tablet orally once daily during cycle 2 (cycle = 28 days).
    Measure Participants 15
    SOF
    2.50
    GS-566500
    4.00
    GS-331007
    4.00
    VEL
    4.00
    VOX
    6.00
    22. Secondary Outcome
    Title PK Parameter: Tlast of SOF, SOF Metabolites (GS-566500 and GS-331007), VEL, and VOX
    Description Tlast is defined as the time (observed time point) of Clast.
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    Participants in the PK Analysis Set who were enrolled in Part B and received NGM+ SOV/VEL/VOX + VOX were analyzed.
    Arm/Group Title Part B: NGM/EE + SOF/VEL/VOX + VOX
    Arm/Group Description Participants received NGM 0.180 mg/0.215 mg/0.25 mg/ EE 0.025 mg + sofosbuvir (SOF)/velpatasvir (VEL)/voxilaprevir (VOX) FDC 400/100/100 mg tablet + VOX 100 mg tablet orally once daily during cycle 2 (cycle = 28 days).
    Measure Participants 15
    SOF
    6.00
    GS-566500
    16.00
    GS-331007
    24.00
    VEL
    24.00
    VOX
    24.00
    23. Secondary Outcome
    Title PK Parameter: Ctau of SOF Metabolites (GS-566500 and GS-331007), VEL, and VOX
    Description Ctau is defined as the observed drug concentration at the end of the dosing interval.
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    Participants in the PK Analysis Set who were enrolled in Part B and received NGM+ SOV/VEL/VOX + VOX were analyzed.
    Arm/Group Title Part B: NGM/EE + SOF/VEL/VOX + VOX
    Arm/Group Description Participants received NGM 0.180 mg/0.215 mg/0.25 mg/ EE 0.025 mg + sofosbuvir (SOF)/velpatasvir (VEL)/voxilaprevir (VOX) FDC 400/100/100 mg tablet + VOX 100 mg tablet orally once daily during cycle 2 (cycle = 28 days).
    Measure Participants 15
    GS-566500
    10.6
    (NA)
    GS-331007
    323.1
    (67.24)
    VEL
    154.6
    (46.71)
    VOX
    56.1
    (59.02)
    24. Secondary Outcome
    Title PK Parameter: λz of SOF, SOF Metabolites (GS-566500 and GS-331007), VEL, and VOX
    Description 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.
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    Participants in the PK Analysis Set who were enrolled in Part B and received NGM+ SOV/VEL/VOX + VOX were analyzed.
    Arm/Group Title Part B: NGM/EE + SOF/VEL/VOX + VOX
    Arm/Group Description Participants received NGM 0.180 mg/0.215 mg/0.25 mg/ EE 0.025 mg + sofosbuvir (SOF)/velpatasvir (VEL)/voxilaprevir (VOX) FDC 400/100/100 mg tablet + VOX 100 mg tablet orally once daily during cycle 2 (cycle = 28 days).
    Measure Participants 15
    SOF
    1.160
    (0.4753)
    GS-566500
    0.247
    (0.0247)
    GS-331007
    0.020
    (0.0091)
    VEL
    0.037
    (0.0103)
    VOX
    0.077
    (0.0277)
    25. Secondary Outcome
    Title PK Parameter: AUCtau of SOF, SOF Metabolites (GS-566500 and GS-331007), VEL, and VOX
    Description AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    Participants in the PK Analysis Set who were enrolled in Part B and received NGM+ SOV/VEL/VOX + VOX were analyzed.
    Arm/Group Title Part B: NGM/EE + SOF/VEL/VOX + VOX
    Arm/Group Description Participants received NGM 0.180 mg/0.215 mg/0.25 mg/ EE 0.025 mg + sofosbuvir (SOF)/velpatasvir (VEL)/voxilaprevir (VOX) FDC 400/100/100 mg tablet + VOX 100 mg tablet orally once daily during cycle 2 (cycle = 28 days).
    Measure Participants 15
    SOF
    1997.2
    (802.99)
    GS-566500
    2769.3
    (446.51)
    GS-331007
    12098.9
    (1929.14)
    VEL
    8226.3
    (2056.25)
    VOX
    3857.9
    (1216.12)
    26. Secondary Outcome
    Title PK Parameter: CLss/F of SOF, VEL, and VOX
    Description CLss/F is defined as the apparent steady state oral clearance following administration of the drug.
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    Participants in the PK Analysis Set who were enrolled in Part B and received NGM+ SOV/VEL/VOX + VOX were analyzed.
    Arm/Group Title Part B: NGM/EE + SOF/VEL/VOX + VOX
    Arm/Group Description Participants received NGM 0.180 mg/0.215 mg/0.25 mg/ EE 0.025 mg + sofosbuvir (SOF)/velpatasvir (VEL)/voxilaprevir (VOX) FDC 400/100/100 mg tablet + VOX 100 mg tablet orally once daily during cycle 2 (cycle = 28 days).
    Measure Participants 15
    SOF
    218383.1
    (53265.75)
    VEL
    12757.3
    (2673.70)
    VOX
    56071.5
    (15234.72)
    27. Secondary Outcome
    Title PK Parameter: t1/2 of SOF, SOF Metabolites (GS-566500 and GS-331007), VEL, and VOX
    Description t1/2 is defined as the estimate of the terminal elimination half-life of the drug.
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    Participants in the PK Analysis Set who were enrolled in Part B and received NGM+ SOV/VEL/VOX + VOX were analyzed.
    Arm/Group Title Part B: NGM/EE + SOF/VEL/VOX + VOX
    Arm/Group Description Participants received NGM 0.180 mg/0.215 mg/0.25 mg/ EE 0.025 mg + sofosbuvir (SOF)/velpatasvir (VEL)/voxilaprevir (VOX) FDC 400/100/100 mg tablet + VOX 100 mg tablet orally once daily during cycle 2 (cycle = 28 days).
    Measure Participants 15
    SOF
    0.68
    GS-566500
    2.70
    GS-331007
    30.06
    VEL
    19.75
    VOX
    8.51

    Adverse Events

    Time Frame First dose date up to the last dose date (maximum: 84 days) plus 10 days
    Adverse Event Reporting Description The Safety Analysis Set included all enrolled participants who took at least 1 dose of study drug.
    Arm/Group Title Part A: NGM/EE Part B: NGM/EE + SOF/VEL/VOX + VOX
    Arm/Group Description Participants received NGM 0.180 mg/0.215 mg/0.25 mg/ EE 0.025 mg tablet orally once daily for 1 cycle (cycle = 28 days). Participants received NGM 0.180 mg/0.215 mg/0.25 mg/ EE 0.025 mg + sofosbuvir (SOF)/velpatasvir (VEL)/voxilaprevir (VOX) FDC 400/100/100 mg tablet + VOX 100 mg orally once daily for 2 cycles (cycle = 28 days).
    All Cause Mortality
    Part A: NGM/EE Part B: NGM/EE + SOF/VEL/VOX + VOX
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/15 (0%) 0/15 (0%)
    Serious Adverse Events
    Part A: NGM/EE Part B: NGM/EE + SOF/VEL/VOX + VOX
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/15 (0%) 0/15 (0%)
    Other (Not Including Serious) Adverse Events
    Part A: NGM/EE Part B: NGM/EE + SOF/VEL/VOX + VOX
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 10/15 (66.7%) 14/15 (93.3%)
    Gastrointestinal disorders
    Abdominal discomfort 0/15 (0%) 1/15 (6.7%)
    Abdominal pain 0/15 (0%) 3/15 (20%)
    Diarrhoea 2/15 (13.3%) 5/15 (33.3%)
    Flatulence 0/15 (0%) 2/15 (13.3%)
    Gingival ulceration 0/15 (0%) 1/15 (6.7%)
    Nausea 1/15 (6.7%) 9/15 (60%)
    Vomiting 0/15 (0%) 3/15 (20%)
    General disorders
    Chills 1/15 (6.7%) 0/15 (0%)
    Fatigue 0/15 (0%) 3/15 (20%)
    Immune system disorders
    Hypersensitivity 1/15 (6.7%) 0/15 (0%)
    Infections and infestations
    Oral herpes 0/15 (0%) 1/15 (6.7%)
    Upper respiratory tract infection 2/15 (13.3%) 0/15 (0%)
    Urinary tract infection 1/15 (6.7%) 0/15 (0%)
    Injury, poisoning and procedural complications
    Arthropod bite 1/15 (6.7%) 0/15 (0%)
    Skin abrasion 0/15 (0%) 1/15 (6.7%)
    Musculoskeletal and connective tissue disorders
    Pain in extremity 0/15 (0%) 1/15 (6.7%)
    Nervous system disorders
    Dizziness 2/15 (13.3%) 0/15 (0%)
    Headache 6/15 (40%) 6/15 (40%)
    Presyncope 1/15 (6.7%) 0/15 (0%)
    Reproductive system and breast disorders
    Metrorrhagia 1/15 (6.7%) 1/15 (6.7%)
    Respiratory, thoracic and mediastinal disorders
    Nasal congestion 1/15 (6.7%) 0/15 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or The study has been completed at all study sites for at least 2 years

    Results Point of Contact

    Name/Title Gilead Clinical Study Information Center
    Organization Gilead Sciences
    Phone 1-833-445-3230 (GILEAD-0)
    Email GileadClinicalTrials@gilead.com
    Responsible Party:
    Gilead Sciences
    ClinicalTrials.gov Identifier:
    NCT02533427
    Other Study ID Numbers:
    • GS-US-367-1909
    First Posted:
    Aug 26, 2015
    Last Update Posted:
    Sep 2, 2020
    Last Verified:
    Aug 1, 2020