Study to Evaluate Effect of Sofosbuvir/Velpatasvir/GS-9857 Fixed-Dose Combination on the Pharmacokinetics of a Representative Hormonal Contraceptive Medication, Norgestimate/Ethinyl Estradiol
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
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:
Drug: VOX
100 mg tablet administered orally once daily
Other Names:
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:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- Percentage of Participants Who Experienced Treatment-Emergent Adverse Events [First dose date up to the last dose date (maximum: 84 days) plus 10 days]
- Percentage of Participants Who Experienced Laboratory Abnormalities [First dose date up to the last dose date (maximum: 84 days) plus 10 days]
Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. The most severe graded abnormality from all tests was counted for each participant. Grade 1: mild; Grade 2: moderate;Grade 3: severe or medically significant but not immediately life-threatening; Grade 4: life-threatening consequences.
- PK Parameter: Tmax of Norelgestromin, Norgestrel, Ethinyl Estradiol, and Norgestimate [Cycle 1,Study Day 14: Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours postdose; Cycle 2,Study Day 42: Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours postdose]
Tmax is defined as the time (observed time point) of Cmax.
- PK Parameter: 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.
- PK Parameter: AUCtau of SOF, SOF Metabolites (GS-566500 and GS-331007), VEL, and VOX [Cycle 2, Study Day 42: Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours postdose]
AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
- PK Parameter: CLss/F of SOF, VEL, and VOX [Cycle 2, Study Day 42: Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours postdose]
CLss/F is defined as the apparent steady state oral clearance following administration of the drug.
- PK Parameter: 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
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.- GS-US-367-1909
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
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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)
|
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
|
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
|
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
|
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
|
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)
|
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
|
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)
|
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)
|
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
|
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
|
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)
|
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)
|
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)
|
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)
|
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
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) |
GileadClinicalTrials@gilead.com |
- GS-US-367-1909