HCV Infection
Conditions
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.
Interventions
DRUGSOF/VEL/VOX
400/100/100 mg FDC tablet administered orally once daily
DRUGVOX
100 mg tablet administered orally once daily
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
Sponsors
Gilead Sciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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: 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). |
| 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: 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: 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 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: 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: 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
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| Percentage of Participants Who Experienced Treatment-Emergent Adverse Events | First dose date up to the last dose date (maximum: 84 days) plus 10 days | — |
| 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. |
| 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. |
| 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: 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: 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: 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: 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: 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: 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: 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: 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. |
Countries
New Zealand
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 details
15 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| NGM/EE + SOF/VEL/VOX + VOX (Part A and Part B) 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). | 15 |
| Total | 15 |
Baseline characteristics
| Characteristic | NGM/EE + SOF/VEL/VOX + VOX (Part A and Part B) |
|---|---|
| Age, Continuous | 24 years STANDARD_DEVIATION 4.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 14 Participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 15 |
| other Total, other adverse events | 10 / 15 | 14 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 |
Outcome results
Primary
Pharmacokinetic (PK) Parameter: AUCtau of Norelgestromin
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: NGM/EE | Pharmacokinetic (PK) Parameter: AUCtau of Norelgestromin | 13757.4 hours*picogram/milliliter (h*pg/mL) | Standard Deviation 2478.44 |
| Part B: NGM/EE + SOF/VEL/VOX + VOX | Pharmacokinetic (PK) Parameter: AUCtau of Norelgestromin | 14690.4 hours*picogram/milliliter (h*pg/mL) | Standard Deviation 2116.43 |
Comparison: Norelgestromin Part B/Part A90% CI: [103.19, 111.69]
Primary
Pharmacokinetic (PK) Parameter: AUCtau of Norgestimate
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
Population: Participants in the PK Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: NGM/EE | Pharmacokinetic (PK) Parameter: AUCtau of Norgestimate | 0.2 h*ng/mL | — |
| Part B: NGM/EE + SOF/VEL/VOX + VOX | Pharmacokinetic (PK) Parameter: AUCtau of Norgestimate | 0.5 h*ng/mL | Standard Deviation 0.48 |
Comparison: Norgestimate Part B/Part A90% CI: [33.11, 1870.81]
Primary
PK Parameter: AUCtau of Ethinyl Estradiol
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
Population: Participants in the PK Analysis Set were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: NGM/EE | PK Parameter: AUCtau of Ethinyl Estradiol | 835.2 h*pg/mL | Standard Deviation 367.17 |
| Part B: NGM/EE + SOF/VEL/VOX + VOX | PK Parameter: AUCtau of Ethinyl Estradiol | 871.4 h*pg/mL | Standard Deviation 355.33 |
Comparison: Ethinyl estradiol Part B/Part A90% CI: [96.95, 114.66]
Primary
PK Parameter: AUCtau of Norgestrel
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
Population: Participants in the PK Analysis Set were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: NGM/EE | PK Parameter: AUCtau of Norgestrel | 41.1 hours*nanogram/milliliter (h*ng/mL) | Standard Deviation 11.05 |
| Part B: NGM/EE + SOF/VEL/VOX + VOX | PK Parameter: AUCtau of Norgestrel | 47.3 hours*nanogram/milliliter (h*ng/mL) | Standard Deviation 13.19 |
Comparison: Norgestrel Part B/Part A90% CI: [106.49, 124.5]
Primary
PK Parameter: Cmax of Ethinyl Estradiol
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
Population: Participants in the PK Analysis Set were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: NGM/EE | PK Parameter: Cmax of Ethinyl Estradiol | 68.4 pg/mL | Standard Deviation 31.06 |
| Part B: NGM/EE + SOF/VEL/VOX + VOX | PK Parameter: Cmax of Ethinyl Estradiol | 80.6 pg/mL | Standard Deviation 28.44 |
Comparison: Ethinyl estradiol Part B/Part A90% CI: [106.1, 138.12]
Primary
PK Parameter: Cmax of Norelgestromin
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
Population: Participants in the PK Analysis Set were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: NGM/EE | PK Parameter: Cmax of Norelgestromin | 1080.9 pg/mL | Standard Deviation 221.11 |
| Part B: NGM/EE + SOF/VEL/VOX + VOX | PK Parameter: Cmax of Norelgestromin | 1162.2 pg/mL | Standard Deviation 209.53 |
Comparison: Norelgestromin Part B/Part A90% CI: [97.78, 118.65]
Primary
PK Parameter: Cmax of Norgestimate
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
Population: Participants in the PK Analysis Set were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: NGM/EE | PK Parameter: Cmax of Norgestimate | 0.0 ng/mL | Standard Deviation 0.04 |
| Part B: NGM/EE + SOF/VEL/VOX + VOX | PK Parameter: Cmax of Norgestimate | 0.1 ng/mL | Standard Deviation 0.05 |
Comparison: Norgestimate Part B/Part A90% CI: [87.19, 144.14]
Primary
PK Parameter: Cmax of Norgestrel
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
Population: Participants in the PK Analysis Set were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: NGM/EE | PK Parameter: Cmax of Norgestrel | 2.0 ng/mL | Standard Deviation 0.52 |
| Part B: NGM/EE + SOF/VEL/VOX + VOX | PK Parameter: Cmax of Norgestrel | 2.3 ng/mL | Standard Deviation 0.61 |
Comparison: Norgestrel Part B/Part A90% CI: [108.12, 122.37]
Primary
PK Parameter: Ctau of Ethinyl Estradiol
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
Population: Participants in the PK Analysis Set were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: NGM/EE | PK Parameter: Ctau of Ethinyl Estradiol | 19.7 pg/mL | Standard Deviation 10.82 |
| Part B: NGM/EE + SOF/VEL/VOX + VOX | PK Parameter: Ctau of Ethinyl Estradiol | 18.2 pg/mL | Standard Deviation 10.39 |
Comparison: Ethinyl estradiol Part B/Part A90% CI: [82.55, 104.45]
Primary
PK Parameter: Ctau of Norelgestromin
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
Population: Participants in the PK Analysis Set were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: NGM/EE | PK Parameter: Ctau of Norelgestromin | 364.1 picogram/milliliter (pg/mL) | Standard Deviation 76.74 |
| Part B: NGM/EE + SOF/VEL/VOX + VOX | PK Parameter: Ctau of Norelgestromin | 413.9 picogram/milliliter (pg/mL) | Standard Deviation 73.78 |
Comparison: Norelgestromin Part B/Part A90% CI: [107.4, 121.39]
Primary
PK Parameter: Ctau of Norgestimate
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
Population: Participants in the PK Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: NGM/EE | PK Parameter: Ctau of Norgestimate | 0.0 ng/mL | Standard Deviation 0 |
| Part B: NGM/EE + SOF/VEL/VOX + VOX | PK Parameter: Ctau of Norgestimate | 0.0 ng/mL | Standard Deviation 0 |
Primary
PK Parameter: Ctau of Norgestrel
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
Population: Participants in the PK Analysis Set were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: NGM/EE | PK Parameter: Ctau of Norgestrel | 1.5 nanogram/milliliter (ng/mL) | Standard Deviation 0.37 |
| Part B: NGM/EE + SOF/VEL/VOX + VOX | PK Parameter: Ctau of Norgestrel | 1.8 nanogram/milliliter (ng/mL) | Standard Deviation 0.55 |
Comparison: Norgestrel Part B/Part A90% CI: [110.85, 133.44]
Secondary
Percentage of Participants Who Experienced Laboratory Abnormalities
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
Population: Participants in the Safety Analysis Set were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: NGM/EE | Percentage of Participants Who Experienced Laboratory Abnormalities | Grade 1 | 60.0 percentage of participants |
| Part A: NGM/EE | Percentage of Participants Who Experienced Laboratory Abnormalities | Grade 2 | 13.3 percentage of participants |
| Part A: NGM/EE | Percentage of Participants Who Experienced Laboratory Abnormalities | Grade 3 | 13.3 percentage of participants |
| Part A: NGM/EE | Percentage of Participants Who Experienced Laboratory Abnormalities | Grade 4 | 0.0 percentage of participants |
| Part B: NGM/EE + SOF/VEL/VOX + VOX | Percentage of Participants Who Experienced Laboratory Abnormalities | Grade 4 | 0.0 percentage of participants |
| Part B: NGM/EE + SOF/VEL/VOX + VOX | Percentage of Participants Who Experienced Laboratory Abnormalities | Grade 1 | 53.3 percentage of participants |
| Part B: NGM/EE + SOF/VEL/VOX + VOX | Percentage of Participants Who Experienced Laboratory Abnormalities | Grade 3 | 0.0 percentage of participants |
| Part B: NGM/EE + SOF/VEL/VOX + VOX | Percentage of Participants Who Experienced Laboratory Abnormalities | Grade 2 | 6.7 percentage of participants |
Secondary
Percentage of Participants Who Experienced Treatment-Emergent Adverse Events
Time frame: First dose date up to the last dose date (maximum: 84 days) plus 10 days
Population: The Safety Analysis Set included all enrolled participants who took at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: NGM/EE | Percentage of Participants Who Experienced Treatment-Emergent Adverse Events | 66.7 percentage of participants |
| Part B: NGM/EE + SOF/VEL/VOX + VOX | Percentage of Participants Who Experienced Treatment-Emergent Adverse Events | 93.3 percentage of participants |
Secondary
PK Parameter: AUCtau of SOF, SOF Metabolites (GS-566500 and GS-331007), VEL, and VOX
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
Population: Participants in the PK Analysis Set who were enrolled in Part B and received NGM+ SOV/VEL/VOX + VOX were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: NGM/EE | PK Parameter: AUCtau of SOF, SOF Metabolites (GS-566500 and GS-331007), VEL, and VOX | SOF | 1997.2 h*ng/mL | Standard Deviation 802.99 |
| Part A: NGM/EE | PK Parameter: AUCtau of SOF, SOF Metabolites (GS-566500 and GS-331007), VEL, and VOX | GS-566500 | 2769.3 h*ng/mL | Standard Deviation 446.51 |
| Part A: NGM/EE | PK Parameter: AUCtau of SOF, SOF Metabolites (GS-566500 and GS-331007), VEL, and VOX | GS-331007 | 12098.9 h*ng/mL | Standard Deviation 1929.14 |
| Part A: NGM/EE | PK Parameter: AUCtau of SOF, SOF Metabolites (GS-566500 and GS-331007), VEL, and VOX | VEL | 8226.3 h*ng/mL | Standard Deviation 2056.25 |
| Part A: NGM/EE | PK Parameter: AUCtau of SOF, SOF Metabolites (GS-566500 and GS-331007), VEL, and VOX | VOX | 3857.9 h*ng/mL | Standard Deviation 1216.12 |
Secondary
PK Parameter: CLss/F Ethinyl Estradiol, and Norgestimate
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
Population: Participants in the PK Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: NGM/EE | PK Parameter: CLss/F Ethinyl Estradiol, and Norgestimate | Ethinyl Estradiol | 34226.8 milliliter/hour (mL/h) | Standard Deviation 12691.91 |
| Part A: NGM/EE | PK Parameter: CLss/F Ethinyl Estradiol, and Norgestimate | Norgestimate | 1285855.5 milliliter/hour (mL/h) | — |
| Part B: NGM/EE + SOF/VEL/VOX + VOX | PK Parameter: CLss/F Ethinyl Estradiol, and Norgestimate | Ethinyl Estradiol | 32000.0 milliliter/hour (mL/h) | Standard Deviation 9530.52 |
| Part B: NGM/EE + SOF/VEL/VOX + VOX | PK Parameter: CLss/F Ethinyl Estradiol, and Norgestimate | Norgestimate | 617498.8 milliliter/hour (mL/h) | Standard Deviation 350620.05 |
Secondary
PK Parameter: CLss/F of SOF, VEL, and VOX
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
Population: Participants in the PK Analysis Set who were enrolled in Part B and received NGM+ SOV/VEL/VOX + VOX were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: NGM/EE | PK Parameter: CLss/F of SOF, VEL, and VOX | SOF | 218383.1 mL/h | Standard Deviation 53265.75 |
| Part A: NGM/EE | PK Parameter: CLss/F of SOF, VEL, and VOX | VEL | 12757.3 mL/h | Standard Deviation 2673.7 |
| Part A: NGM/EE | PK Parameter: CLss/F of SOF, VEL, and VOX | VOX | 56071.5 mL/h | Standard Deviation 15234.72 |
Secondary
PK Parameter: Cmax of Sofosbuvir (SOF), SOF Metabolites (GS-566500 and GS-331007), Velpatasvir (VEL), and Voxilaprevir (VOX)
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
Population: Participants in the PK Analysis Set who were enrolled in Part B and received NGM+ SOV/VEL/VOX + VOX were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: NGM/EE | PK Parameter: Cmax of Sofosbuvir (SOF), SOF Metabolites (GS-566500 and GS-331007), Velpatasvir (VEL), and Voxilaprevir (VOX) | SOF | 967.6 ng/mL | Standard Deviation 322.2 |
| Part A: NGM/EE | PK Parameter: Cmax of Sofosbuvir (SOF), SOF Metabolites (GS-566500 and GS-331007), Velpatasvir (VEL), and Voxilaprevir (VOX) | GS-566500 | 491.1 ng/mL | Standard Deviation 107.66 |
| Part A: NGM/EE | PK Parameter: Cmax of Sofosbuvir (SOF), SOF Metabolites (GS-566500 and GS-331007), Velpatasvir (VEL), and Voxilaprevir (VOX) | GS-331007 | 979.4 ng/mL | Standard Deviation 119.43 |
| Part A: NGM/EE | PK Parameter: Cmax of Sofosbuvir (SOF), SOF Metabolites (GS-566500 and GS-331007), Velpatasvir (VEL), and Voxilaprevir (VOX) | VEL | 853.3 ng/mL | Standard Deviation 161.6 |
| Part A: NGM/EE | PK Parameter: Cmax of Sofosbuvir (SOF), SOF Metabolites (GS-566500 and GS-331007), Velpatasvir (VEL), and Voxilaprevir (VOX) | VOX | 512.4 ng/mL | Standard Deviation 171.71 |
Secondary
PK Parameter: Ctau of SOF Metabolites (GS-566500 and GS-331007), VEL, and VOX
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
Population: Participants in the PK Analysis Set who were enrolled in Part B and received NGM+ SOV/VEL/VOX + VOX were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: NGM/EE | PK Parameter: Ctau of SOF Metabolites (GS-566500 and GS-331007), VEL, and VOX | GS-566500 | 10.6 ng/mL | — |
| Part A: NGM/EE | PK Parameter: Ctau of SOF Metabolites (GS-566500 and GS-331007), VEL, and VOX | GS-331007 | 323.1 ng/mL | Standard Deviation 67.24 |
| Part A: NGM/EE | PK Parameter: Ctau of SOF Metabolites (GS-566500 and GS-331007), VEL, and VOX | VEL | 154.6 ng/mL | Standard Deviation 46.71 |
| Part A: NGM/EE | PK Parameter: Ctau of SOF Metabolites (GS-566500 and GS-331007), VEL, and VOX | VOX | 56.1 ng/mL | Standard Deviation 59.02 |
Secondary
PK Parameter: t1/2 of Norelgestromin, Norgestrel, Ethinyl Estradiol, and Norgestimate
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
Population: Participants in the PK Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A: NGM/EE | PK Parameter: t1/2 of Norelgestromin, Norgestrel, Ethinyl Estradiol, and Norgestimate | Norelgestromin | 18.91 hours |
| Part A: NGM/EE | PK Parameter: t1/2 of Norelgestromin, Norgestrel, Ethinyl Estradiol, and Norgestimate | Norgestrel | 33.76 hours |
| Part A: NGM/EE | PK Parameter: t1/2 of Norelgestromin, Norgestrel, Ethinyl Estradiol, and Norgestimate | Ethinyl Estradiol | 13.68 hours |
| Part A: NGM/EE | PK Parameter: t1/2 of Norelgestromin, Norgestrel, Ethinyl Estradiol, and Norgestimate | Norgestimate | 1.03 hours |
| Part B: NGM/EE + SOF/VEL/VOX + VOX | PK Parameter: t1/2 of Norelgestromin, Norgestrel, Ethinyl Estradiol, and Norgestimate | Norgestimate | 2.30 hours |
| Part B: NGM/EE + SOF/VEL/VOX + VOX | PK Parameter: t1/2 of Norelgestromin, Norgestrel, Ethinyl Estradiol, and Norgestimate | Norelgestromin | 28.95 hours |
| Part B: NGM/EE + SOF/VEL/VOX + VOX | PK Parameter: t1/2 of Norelgestromin, Norgestrel, Ethinyl Estradiol, and Norgestimate | Ethinyl Estradiol | 10.78 hours |
| Part B: NGM/EE + SOF/VEL/VOX + VOX | PK Parameter: t1/2 of Norelgestromin, Norgestrel, Ethinyl Estradiol, and Norgestimate | Norgestrel | 57.42 hours |
Secondary
PK Parameter: t1/2 of SOF, SOF Metabolites (GS-566500 and GS-331007), VEL, and VOX
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
Population: Participants in the PK Analysis Set who were enrolled in Part B and received NGM+ SOV/VEL/VOX + VOX were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A: NGM/EE | PK Parameter: t1/2 of SOF, SOF Metabolites (GS-566500 and GS-331007), VEL, and VOX | SOF | 0.68 hours |
| Part A: NGM/EE | PK Parameter: t1/2 of SOF, SOF Metabolites (GS-566500 and GS-331007), VEL, and VOX | GS-566500 | 2.70 hours |
| Part A: NGM/EE | PK Parameter: t1/2 of SOF, SOF Metabolites (GS-566500 and GS-331007), VEL, and VOX | GS-331007 | 30.06 hours |
| Part A: NGM/EE | PK Parameter: t1/2 of SOF, SOF Metabolites (GS-566500 and GS-331007), VEL, and VOX | VEL | 19.75 hours |
| Part A: NGM/EE | PK Parameter: t1/2 of SOF, SOF Metabolites (GS-566500 and GS-331007), VEL, and VOX | VOX | 8.51 hours |
Secondary
PK Parameter: Tlast of Norelgestromin, Norgestrel, Ethinyl Estradiol, and Norgestimate
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
Population: Participants in the PK Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A: NGM/EE | PK Parameter: Tlast of Norelgestromin, Norgestrel, Ethinyl Estradiol, and Norgestimate | Norgestrel | 24.00 hours |
| Part A: NGM/EE | PK Parameter: Tlast of Norelgestromin, Norgestrel, Ethinyl Estradiol, and Norgestimate | Norelgestromin | 24.00 hours |
| Part A: NGM/EE | PK Parameter: Tlast of Norelgestromin, Norgestrel, Ethinyl Estradiol, and Norgestimate | Ethinyl Estradiol | 24.00 hours |
| Part A: NGM/EE | PK Parameter: Tlast of Norelgestromin, Norgestrel, Ethinyl Estradiol, and Norgestimate | Norgestimate | 1.50 hours |
| Part B: NGM/EE + SOF/VEL/VOX + VOX | PK Parameter: Tlast of Norelgestromin, Norgestrel, Ethinyl Estradiol, and Norgestimate | Norgestimate | 2.75 hours |
| Part B: NGM/EE + SOF/VEL/VOX + VOX | PK Parameter: Tlast of Norelgestromin, Norgestrel, Ethinyl Estradiol, and Norgestimate | Ethinyl Estradiol | 24.00 hours |
| Part B: NGM/EE + SOF/VEL/VOX + VOX | PK Parameter: Tlast of Norelgestromin, Norgestrel, Ethinyl Estradiol, and Norgestimate | Norelgestromin | 24.00 hours |
| Part B: NGM/EE + SOF/VEL/VOX + VOX | PK Parameter: Tlast of Norelgestromin, Norgestrel, Ethinyl Estradiol, and Norgestimate | Norgestrel | 24.00 hours |
Secondary
PK Parameter: Tlast of SOF, SOF Metabolites (GS-566500 and GS-331007), VEL, and VOX
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
Population: Participants in the PK Analysis Set who were enrolled in Part B and received NGM+ SOV/VEL/VOX + VOX were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A: NGM/EE | PK Parameter: Tlast of SOF, SOF Metabolites (GS-566500 and GS-331007), VEL, and VOX | SOF | 6.00 hours |
| Part A: NGM/EE | PK Parameter: Tlast of SOF, SOF Metabolites (GS-566500 and GS-331007), VEL, and VOX | GS-566500 | 16.00 hours |
| Part A: NGM/EE | PK Parameter: Tlast of SOF, SOF Metabolites (GS-566500 and GS-331007), VEL, and VOX | GS-331007 | 24.00 hours |
| Part A: NGM/EE | PK Parameter: Tlast of SOF, SOF Metabolites (GS-566500 and GS-331007), VEL, and VOX | VEL | 24.00 hours |
| Part A: NGM/EE | PK Parameter: Tlast of SOF, SOF Metabolites (GS-566500 and GS-331007), VEL, and VOX | VOX | 24.00 hours |
Secondary
PK Parameter: Tmax of Norelgestromin, Norgestrel, Ethinyl Estradiol, and Norgestimate
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
Population: Participants in the PK Analysis Set with available were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A: NGM/EE | PK Parameter: Tmax of Norelgestromin, Norgestrel, Ethinyl Estradiol, and Norgestimate | Norelgestromin | 3.00 hours |
| Part A: NGM/EE | PK Parameter: Tmax of Norelgestromin, Norgestrel, Ethinyl Estradiol, and Norgestimate | Norgestrel | 4.00 hours |
| Part A: NGM/EE | PK Parameter: Tmax of Norelgestromin, Norgestrel, Ethinyl Estradiol, and Norgestimate | Ethinyl Estradiol | 3.00 hours |
| Part A: NGM/EE | PK Parameter: Tmax of Norelgestromin, Norgestrel, Ethinyl Estradiol, and Norgestimate | Norgestimate | 1.50 hours |
| Part B: NGM/EE + SOF/VEL/VOX + VOX | PK Parameter: Tmax of Norelgestromin, Norgestrel, Ethinyl Estradiol, and Norgestimate | Norgestimate | 1.50 hours |
| Part B: NGM/EE + SOF/VEL/VOX + VOX | PK Parameter: Tmax of Norelgestromin, Norgestrel, Ethinyl Estradiol, and Norgestimate | Norelgestromin | 3.00 hours |
| Part B: NGM/EE + SOF/VEL/VOX + VOX | PK Parameter: Tmax of Norelgestromin, Norgestrel, Ethinyl Estradiol, and Norgestimate | Ethinyl Estradiol | 2.00 hours |
| Part B: NGM/EE + SOF/VEL/VOX + VOX | PK Parameter: Tmax of Norelgestromin, Norgestrel, Ethinyl Estradiol, and Norgestimate | Norgestrel | 4.00 hours |
Secondary
PK Parameter: Tmax of SOF, SOF Metabolites (GS-566500 and GS-331007), VEL, and VOX
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
Population: Participants in the PK Analysis Set who were enrolled in Part B and received NGM+ SOV/VEL/VOX + VOX were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A: NGM/EE | PK Parameter: Tmax of SOF, SOF Metabolites (GS-566500 and GS-331007), VEL, and VOX | SOF | 2.50 hours |
| Part A: NGM/EE | PK Parameter: Tmax of SOF, SOF Metabolites (GS-566500 and GS-331007), VEL, and VOX | GS-566500 | 4.00 hours |
| Part A: NGM/EE | PK Parameter: Tmax of SOF, SOF Metabolites (GS-566500 and GS-331007), VEL, and VOX | GS-331007 | 4.00 hours |
| Part A: NGM/EE | PK Parameter: Tmax of SOF, SOF Metabolites (GS-566500 and GS-331007), VEL, and VOX | VEL | 4.00 hours |
| Part A: NGM/EE | PK Parameter: Tmax of SOF, SOF Metabolites (GS-566500 and GS-331007), VEL, and VOX | VOX | 6.00 hours |
Secondary
PK Parameter: λz of Norelgestromin, Norgestrel, Ethinyl Estradiol, and Norgestimate
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
Population: Participants in the PK Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: NGM/EE | PK Parameter: λz of Norelgestromin, Norgestrel, Ethinyl Estradiol, and Norgestimate | Norelgestromin | 0.035 1/hours (1/h) | Standard Deviation 0.0095 |
| Part A: NGM/EE | PK Parameter: λz of Norelgestromin, Norgestrel, Ethinyl Estradiol, and Norgestimate | Norgestrel | 0.016 1/hours (1/h) | Standard Deviation 0.0081 |
| Part A: NGM/EE | PK Parameter: λz of Norelgestromin, Norgestrel, Ethinyl Estradiol, and Norgestimate | Ethinyl Estradiol | 0.053 1/hours (1/h) | Standard Deviation 0.023 |
| Part A: NGM/EE | PK Parameter: λz of Norelgestromin, Norgestrel, Ethinyl Estradiol, and Norgestimate | Norgestimate | 0.674 1/hours (1/h) | — |
| Part B: NGM/EE + SOF/VEL/VOX + VOX | PK Parameter: λz of Norelgestromin, Norgestrel, Ethinyl Estradiol, and Norgestimate | Norgestimate | 0.392 1/hours (1/h) | Standard Deviation 0.3674 |
| Part B: NGM/EE + SOF/VEL/VOX + VOX | PK Parameter: λz of Norelgestromin, Norgestrel, Ethinyl Estradiol, and Norgestimate | Norelgestromin | 0.025 1/hours (1/h) | Standard Deviation 0.0084 |
| Part B: NGM/EE + SOF/VEL/VOX + VOX | PK Parameter: λz of Norelgestromin, Norgestrel, Ethinyl Estradiol, and Norgestimate | Ethinyl Estradiol | 0.059 1/hours (1/h) | Standard Deviation 0.0186 |
| Part B: NGM/EE + SOF/VEL/VOX + VOX | PK Parameter: λz of Norelgestromin, Norgestrel, Ethinyl Estradiol, and Norgestimate | Norgestrel | 0.012 1/hours (1/h) | Standard Deviation 0.0039 |
Secondary
PK Parameter: λz of SOF, SOF Metabolites (GS-566500 and GS-331007), VEL, and VOX
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
Population: Participants in the PK Analysis Set who were enrolled in Part B and received NGM+ SOV/VEL/VOX + VOX were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: NGM/EE | PK Parameter: λz of SOF, SOF Metabolites (GS-566500 and GS-331007), VEL, and VOX | GS-566500 | 0.247 1/h | Standard Deviation 0.0247 |
| Part A: NGM/EE | PK Parameter: λz of SOF, SOF Metabolites (GS-566500 and GS-331007), VEL, and VOX | SOF | 1.160 1/h | Standard Deviation 0.4753 |
| Part A: NGM/EE | PK Parameter: λz of SOF, SOF Metabolites (GS-566500 and GS-331007), VEL, and VOX | GS-331007 | 0.020 1/h | Standard Deviation 0.0091 |
| Part A: NGM/EE | PK Parameter: λz of SOF, SOF Metabolites (GS-566500 and GS-331007), VEL, and VOX | VEL | 0.037 1/h | Standard Deviation 0.0103 |
| Part A: NGM/EE | PK Parameter: λz of SOF, SOF Metabolites (GS-566500 and GS-331007), VEL, and VOX | VOX | 0.077 1/h | Standard Deviation 0.0277 |