Chronic Hepatitis C
Conditions
Brief summary
The purpose of this study is to assess the effect of BMS-790052 on the pharmacokinetics of Ortho Tri-Cyclen® in healthy female subjects.
Interventions
DRUGBMS-790052
Tablets, Oral, 60 mg, once daily, 10 days
Tablets, Oral, once daily, 78 days
Sponsors
Bristol-Myers Squibb
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
Key Inclusion Criteria: * Healthy female subjects, 18-45 years, BMI 18-32 kg/m². * Must be using an adequate method of contraception to avoid pregnancy throughout the study. Key
Exclusion criteria
* Abnormal Pap smear within 1 yr of dosing, and abnormal menstrual cycle during the 3 months prior to enrollment. * Any significant or chronic uncontrolled medical illness.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of Ethinyl Estradiol | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Days 49 and 77 | Ethinyl Estradiol is an analyte of Ortho Tri-Cyclen. Ethinyl Estradiol was measured in plasma, using liquid chromatography-tandem mass spectrometry (LC-MS/MS) by a validated analytical method during the period of known analyte stability. Cmax was measured in picograms per milliliter (pg/mL) and derived from 24 hour plasma concentration versus time data using non-compartmental methods. Pre-dose concentrations and concentrations prior to the first quantifiable concentration that were below the lower limit of quantitation were treated as missing. |
| Area Under the Concentration-Time Curve (AUC) in 1 Dosing Interval of Ethinyl Estradiol | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose on Days 49 and 77 | Ethinyl Estradiol was measured in plasma, using liquid chromatography-tandem mass spectrometry by a validated analytical method during the period of known analyte stability. AUC(TAU) was measured in picograms multiplied by hours (h) per milliliter (pg\*h/mL) and derived from 24 hour plasma concentration versus time data using non-compartmental methods. Pre-dose concentrations and concentrations prior to the first quantifiable concentration that were below the lower limit of quantitation were treated as missing. |
| Time of Maximum Observed Plasma Concentration of Ethinyl Estradiol | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose on Days 49 and 77 | Ethinyl Estradiol was measured in plasma, using liquid chromatography-tandem mass spectrometry by a validated analytical method during the period of known analyte stability. Tmax was measured in hours (h), and derived from 24 hour plasma concentration versus time data using non-compartmental methods. Pre-dose concentrations and concentrations prior to the first quantifiable concentration that were below the lower limit of quantitation were treated as missing. |
| Maximum Observed Plasma Concentration of Norelgestromin | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose on Days 49 and 77 | Norelgestromin is a major active metabolite of norgestimate (NGM) which is found in Ortho Tri-Cyclen. Norelgestromin was measured in plasma, using liquid chromatography-tandem mass spectrometry by a validated analytical method during the period of known analyte stability. Cmax was measured in nanograms per milliliter (ng/mL) and derived from 24 hour plasma concentration versus time data using non-compartmental methods. Pre-dose concentrations and concentrations prior to the first quantifiable concentration that were below the lower limit of quantitation were treated as missing. |
| Area Under the Concentration-Time Curve in 1 Dosing Interval of Norelgestromin | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose on Days 49 and 77 | Norelgestromin was measured in plasma, using liquid chromatography-tandem mass spectrometry by a validated analytical method during the period of known analyte stability. AUC(TAU) was measured in nanograms multiplied by hours (h) per milliliter (ng\*h/mL) and derived from 24 hour plasma concentration versus time data using non-compartmental methods. Pre-dose concentrations and concentrations prior to the first quantifiable concentration that were below the lower limit of quantitation were treated as missing. |
| Time of Maximum Observed Plasma Concentration of Norelgestromin | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose on Days 49 and 77 | Norelgestromin was measured in plasma, using liquid chromatography-tandem mass spectrometry by a validated analytical method during the period of known analyte stability. Tmax was measured in hours (h), and derived from 24 hour plasma concentration versus time data using non-compartmental methods. Pre-dose concentrations and concentrations prior to the first quantifiable concentration that were below the lower limit of quantitation were treated as missing. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration of Norgestrel | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose on Days 49 and 77 | Norgestrel is an NGM metabolite and was measured in plasma using liquid chromatography-mass spectrometry by a validated analytical method during the period of known analyte stability. Cmax was measured in picograms per milliliter (pg/mL) and derived from 24 hour plasma concentration versus time data using non-compartmental methods. Pre-dose concentrations and concentrations prior to the first quantifiable concentration that were below the lower limit of quantitation were treated as missing. |
| Number of Participants Demonstrating a Clinically Meaningful Effect in ECG Parameters | Screening, Day 1, Day 67, Day 77 | The electrocardiogram (ECG) evaluations were performed within ± 15 minutes of the relative time points. ECGs were recorded after the participants were in supine position for at least 5 minutes. ECG parameters measured were: PR interval, QRS complex, QT interval and corrected QT (QTc). |
| Area Under the Concentration-Time Curve in 1 Dosing Interval of Norgestrel | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose on Days 49 and 77 | Norgestrel was measured in plasma, using liquid chromatography-tandem mass spectrometry by a validated analytical method during the period of known analyte stability. AUC(TAU) was measured in picograms multiplied by hours (h) per milliliter (pg\*h/mL) and derived from 24 hour plasma concentration versus time data using non-compartmental methods. Pre-dose concentrations and concentrations prior to the first quantifiable concentration that were below the lower limit of quantitation were treated as missing. |
| Time of Maximum Observed Plasma Concentration of Norgestrel | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose on Days 49 and 77 | Norgestrel was measured in plasma, using liquid chromatography-tandem mass spectrometry by a validated analytical method during the period of known analyte stability. Tmax was measured in hours (h), and derived from 24 hour plasma concentration versus time data using non-compartmental methods. Pre-dose concentrations and concentrations prior to the first quantifiable concentration that were below the lower limit of quantitation were treated as missing. |
| Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Who Died | For AEs from start of treatment (Day 1) up to Day 78 or discharge and for SAEs from Day 1 to 30 days after last dose of study drug | AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. |
| Number of Participants With Laboratory Test Abnormalities | From start of treatment (Day 1) up to Day 78 or discharge | Laboratory marked abnormalities were defined as Hematocrit (low) as \<0.85\*Pre-treatment (PreRx), Hemoglobin (low) as \<0.85\*PreRx, Aspartate Aminotransferase (AST) (high) as \>1.25\*PreRx if PreRx \> upper limits of normal (ULN); \>1.25\*ULN if PreRx \<=ULN; \>1.25\*ULN if PreRx = Missing, Blood in urine (high) as ≥2 PreRx if PreRx ≥1; ≥2 if PreRx \<1; ≥2 if PreRx = Missing. |
| Number of Participants Demonstrating a Clinically Meaningful Effect in Vital Signs | Baseline, Day 28, Day 29, Day 67, Day 68, Day 78, Day of discharge | Vital Signs were measured after the participant was seated quietly for at least 5 minutes and included systolic and diastolic blood pressure, heart rate, respiratory rate, and temperature. Baseline = Last non-missing pretreatment value. |
Countries
Canada, United States
Participant flow
Pre-assignment details
A total of 47 participants were enrolled; 20 were treated. Reasons 27 participants were not treated: 21 no longer met study criteria, 2 withdrew consent, and 4 other reasons.
Participants by arm
| Arm | Count |
|---|---|
| Ortho Tri-Cyclen + Daclatasvir Participants received sequentially Treatment A: Ortho Tri-Cyclen fixed dose combination tablet, orally, once daily up to Day 28, Treatment B: Ortho Tri-Cyclen fixed dose combination tablet, orally, once daily from Day 29 to 56 and Treatment C: Ortho Tri-Cyclen fixed dose combination tablet, orally, once daily from Day 57 to 77 concomitantly with daclatasvir, two tablets of 30-mg, orally, once daily from Day 68 to 77. | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Personal Reasons | 1 |
Baseline characteristics
| Characteristic | Ortho Tri-Cyclen + Daclatasvir |
|---|---|
| Age, Continuous | 29.8 years STANDARD_DEVIATION 7.36 |
| Age, Customized <= 45 years | 20 participants |
| Sex: Female, Male Female | 20 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 16 / 20 | 8 / 20 | 3 / 20 | 7 / 20 | 5 / 18 | 12 / 18 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 | 0 / 20 | 0 / 20 | 0 / 18 | 0 / 18 |
Outcome results
Primary
Area Under the Concentration-Time Curve (AUC) in 1 Dosing Interval of Ethinyl Estradiol
Ethinyl Estradiol was measured in plasma, using liquid chromatography-tandem mass spectrometry by a validated analytical method during the period of known analyte stability. AUC(TAU) was measured in picograms multiplied by hours (h) per milliliter (pg\*h/mL) and derived from 24 hour plasma concentration versus time data using non-compartmental methods. Pre-dose concentrations and concentrations prior to the first quantifiable concentration that were below the lower limit of quantitation were treated as missing.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose on Days 49 and 77
Population: All participants who received the study drug.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ortho Tri-Cyclen | Area Under the Concentration-Time Curve (AUC) in 1 Dosing Interval of Ethinyl Estradiol | 959.37 pg*h/mL | Geometric Coefficient of Variation 38 |
| Ortho Tri-Cyclen + Daclatasvir | Area Under the Concentration-Time Curve (AUC) in 1 Dosing Interval of Ethinyl Estradiol | 994.40 pg*h/mL | Geometric Coefficient of Variation 35 |
Comparison: Mixed effect models were fitted to log-transformed data with treatment as a fixed effect, and measurements within each participant as repeated measurements.90% CI: [0.951, 1.07]
Primary
Area Under the Concentration-Time Curve in 1 Dosing Interval of Norelgestromin
Norelgestromin was measured in plasma, using liquid chromatography-tandem mass spectrometry by a validated analytical method during the period of known analyte stability. AUC(TAU) was measured in nanograms multiplied by hours (h) per milliliter (ng\*h/mL) and derived from 24 hour plasma concentration versus time data using non-compartmental methods. Pre-dose concentrations and concentrations prior to the first quantifiable concentration that were below the lower limit of quantitation were treated as missing.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose on Days 49 and 77
Population: All participants who received the study drug.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ortho Tri-Cyclen | Area Under the Concentration-Time Curve in 1 Dosing Interval of Norelgestromin | 15.38 ng*h/mL | Geometric Coefficient of Variation 24 |
| Ortho Tri-Cyclen + Daclatasvir | Area Under the Concentration-Time Curve in 1 Dosing Interval of Norelgestromin | 16.84 ng*h/mL | Geometric Coefficient of Variation 20 |
Comparison: Mixed effect models were fitted to log-transformed data with treatment as a fixed effect, and measurements within each participant as repeated measurements.90% CI: [1.063, 1.171]
Primary
Maximum Observed Plasma Concentration (Cmax) of Ethinyl Estradiol
Ethinyl Estradiol is an analyte of Ortho Tri-Cyclen. Ethinyl Estradiol was measured in plasma, using liquid chromatography-tandem mass spectrometry (LC-MS/MS) by a validated analytical method during the period of known analyte stability. Cmax was measured in picograms per milliliter (pg/mL) and derived from 24 hour plasma concentration versus time data using non-compartmental methods. Pre-dose concentrations and concentrations prior to the first quantifiable concentration that were below the lower limit of quantitation were treated as missing.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Days 49 and 77
Population: All participants who received the study drug.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ortho Tri-Cyclen | Maximum Observed Plasma Concentration (Cmax) of Ethinyl Estradiol | 118.53 picogram per millilitre (pg/mL) | Geometric Coefficient of Variation 34 |
| Ortho Tri-Cyclen + Daclatasvir | Maximum Observed Plasma Concentration (Cmax) of Ethinyl Estradiol | 134.70 picogram per millilitre (pg/mL) | Geometric Coefficient of Variation 30 |
Comparison: Mixed effect models were fitted to log-transformed data with treatment as a fixed effect, and measurements within each participant as repeated measurements.90% CI: [1.023, 1.195]
Primary
Maximum Observed Plasma Concentration of Norelgestromin
Norelgestromin is a major active metabolite of norgestimate (NGM) which is found in Ortho Tri-Cyclen. Norelgestromin was measured in plasma, using liquid chromatography-tandem mass spectrometry by a validated analytical method during the period of known analyte stability. Cmax was measured in nanograms per milliliter (ng/mL) and derived from 24 hour plasma concentration versus time data using non-compartmental methods. Pre-dose concentrations and concentrations prior to the first quantifiable concentration that were below the lower limit of quantitation were treated as missing.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose on Days 49 and 77
Population: All participants who received the study drug.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ortho Tri-Cyclen | Maximum Observed Plasma Concentration of Norelgestromin | 1.99 nanogram per millilitre (ng/mL) | Geometric Coefficient of Variation 20 |
| Ortho Tri-Cyclen + Daclatasvir | Maximum Observed Plasma Concentration of Norelgestromin | 2.10 nanogram per millilitre (ng/mL) | Geometric Coefficient of Variation 20 |
Comparison: Mixed effect models were fitted to log-transformed data with treatment as a fixed effect, and measurements within each participant as repeated measurements.90% CI: [0.988, 1.135]
Primary
Time of Maximum Observed Plasma Concentration of Ethinyl Estradiol
Ethinyl Estradiol was measured in plasma, using liquid chromatography-tandem mass spectrometry by a validated analytical method during the period of known analyte stability. Tmax was measured in hours (h), and derived from 24 hour plasma concentration versus time data using non-compartmental methods. Pre-dose concentrations and concentrations prior to the first quantifiable concentration that were below the lower limit of quantitation were treated as missing.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose on Days 49 and 77
Population: All participants who received the study drug
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ortho Tri-Cyclen | Time of Maximum Observed Plasma Concentration of Ethinyl Estradiol | 1.5 hours |
| Ortho Tri-Cyclen + Daclatasvir | Time of Maximum Observed Plasma Concentration of Ethinyl Estradiol | 1.5 hours |
Primary
Time of Maximum Observed Plasma Concentration of Norelgestromin
Norelgestromin was measured in plasma, using liquid chromatography-tandem mass spectrometry by a validated analytical method during the period of known analyte stability. Tmax was measured in hours (h), and derived from 24 hour plasma concentration versus time data using non-compartmental methods. Pre-dose concentrations and concentrations prior to the first quantifiable concentration that were below the lower limit of quantitation were treated as missing.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose on Days 49 and 77
Population: All participants who received the study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ortho Tri-Cyclen | Time of Maximum Observed Plasma Concentration of Norelgestromin | 1.3 hours |
| Ortho Tri-Cyclen + Daclatasvir | Time of Maximum Observed Plasma Concentration of Norelgestromin | 1.5 hours |
Secondary
Area Under the Concentration-Time Curve in 1 Dosing Interval of Norgestrel
Norgestrel was measured in plasma, using liquid chromatography-tandem mass spectrometry by a validated analytical method during the period of known analyte stability. AUC(TAU) was measured in picograms multiplied by hours (h) per milliliter (pg\*h/mL) and derived from 24 hour plasma concentration versus time data using non-compartmental methods. Pre-dose concentrations and concentrations prior to the first quantifiable concentration that were below the lower limit of quantitation were treated as missing.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose on Days 49 and 77
Population: All participants who received the study drug.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ortho Tri-Cyclen | Area Under the Concentration-Time Curve in 1 Dosing Interval of Norgestrel | 47258.35 pg*h/mL | Geometric Coefficient of Variation 38 |
| Ortho Tri-Cyclen + Daclatasvir | Area Under the Concentration-Time Curve in 1 Dosing Interval of Norgestrel | 51760.43 pg*h/mL | Geometric Coefficient of Variation 35 |
Comparison: Mixed effect models were fitted to log-transformed data with treatment as a fixed effect, and measurements within each participant as repeated measurements.90% CI: [1.018, 1.234]
Secondary
Maximum Observed Plasma Concentration of Norgestrel
Norgestrel is an NGM metabolite and was measured in plasma using liquid chromatography-mass spectrometry by a validated analytical method during the period of known analyte stability. Cmax was measured in picograms per milliliter (pg/mL) and derived from 24 hour plasma concentration versus time data using non-compartmental methods. Pre-dose concentrations and concentrations prior to the first quantifiable concentration that were below the lower limit of quantitation were treated as missing.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose on Days 49 and 77
Population: All participants who received the study drug.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ortho Tri-Cyclen | Maximum Observed Plasma Concentration of Norgestrel | 2674.69 pg/mL | Geometric Coefficient of Variation 32 |
| Ortho Tri-Cyclen + Daclatasvir | Maximum Observed Plasma Concentration of Norgestrel | 2815.98 pg/mL | Geometric Coefficient of Variation 32 |
Comparison: Mixed effect models were fitted to log-transformed data with treatment as a fixed effect, and measurements within each participant as repeated measurements.90% CI: [0.988, 1.16]
Secondary
Number of Participants Demonstrating a Clinically Meaningful Effect in ECG Parameters
The electrocardiogram (ECG) evaluations were performed within ± 15 minutes of the relative time points. ECGs were recorded after the participants were in supine position for at least 5 minutes. ECG parameters measured were: PR interval, QRS complex, QT interval and corrected QT (QTc).
Time frame: Screening, Day 1, Day 67, Day 77
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ortho Tri-Cyclen | Number of Participants Demonstrating a Clinically Meaningful Effect in ECG Parameters | 0 participants |
| Ortho Tri-Cyclen + Daclatasvir | Number of Participants Demonstrating a Clinically Meaningful Effect in ECG Parameters | 0 participants |
Secondary
Number of Participants Demonstrating a Clinically Meaningful Effect in Vital Signs
Vital Signs were measured after the participant was seated quietly for at least 5 minutes and included systolic and diastolic blood pressure, heart rate, respiratory rate, and temperature. Baseline = Last non-missing pretreatment value.
Time frame: Baseline, Day 28, Day 29, Day 67, Day 68, Day 78, Day of discharge
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ortho Tri-Cyclen | Number of Participants Demonstrating a Clinically Meaningful Effect in Vital Signs | 0 participants |
| Ortho Tri-Cyclen + Daclatasvir | Number of Participants Demonstrating a Clinically Meaningful Effect in Vital Signs | 0 participants |
Secondary
Number of Participants With Laboratory Test Abnormalities
Laboratory marked abnormalities were defined as Hematocrit (low) as \<0.85\*Pre-treatment (PreRx), Hemoglobin (low) as \<0.85\*PreRx, Aspartate Aminotransferase (AST) (high) as \>1.25\*PreRx if PreRx \> upper limits of normal (ULN); \>1.25\*ULN if PreRx \<=ULN; \>1.25\*ULN if PreRx = Missing, Blood in urine (high) as ≥2 PreRx if PreRx ≥1; ≥2 if PreRx \<1; ≥2 if PreRx = Missing.
Time frame: From start of treatment (Day 1) up to Day 78 or discharge
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ortho Tri-Cyclen | Number of Participants With Laboratory Test Abnormalities | Hematocrit | 1 participants |
| Ortho Tri-Cyclen | Number of Participants With Laboratory Test Abnormalities | Hemoglobin | 1 participants |
| Ortho Tri-Cyclen | Number of Participants With Laboratory Test Abnormalities | AST | 1 participants |
| Ortho Tri-Cyclen | Number of Participants With Laboratory Test Abnormalities | Blood in Urine | 0 participants |
| Ortho Tri-Cyclen + Daclatasvir | Number of Participants With Laboratory Test Abnormalities | Blood in Urine | 1 participants |
| Ortho Tri-Cyclen + Daclatasvir | Number of Participants With Laboratory Test Abnormalities | Hematocrit | 0 participants |
| Ortho Tri-Cyclen + Daclatasvir | Number of Participants With Laboratory Test Abnormalities | AST | 0 participants |
| Ortho Tri-Cyclen + Daclatasvir | Number of Participants With Laboratory Test Abnormalities | Hemoglobin | 0 participants |
Secondary
Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Who Died
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.
Time frame: For AEs from start of treatment (Day 1) up to Day 78 or discharge and for SAEs from Day 1 to 30 days after last dose of study drug
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ortho Tri-Cyclen | Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Who Died | SAE | 0 participants |
| Ortho Tri-Cyclen | Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Who Died | AE Leading to Discontinuation | 0 participants |
| Ortho Tri-Cyclen | Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Who Died | Death | 0 participants |
| Ortho Tri-Cyclen + Daclatasvir | Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Who Died | SAE | 0 participants |
| Ortho Tri-Cyclen + Daclatasvir | Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Who Died | AE Leading to Discontinuation | 1 participants |
| Ortho Tri-Cyclen + Daclatasvir | Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Who Died | Death | 0 participants |
Secondary
Time of Maximum Observed Plasma Concentration of Norgestrel
Norgestrel was measured in plasma, using liquid chromatography-tandem mass spectrometry by a validated analytical method during the period of known analyte stability. Tmax was measured in hours (h), and derived from 24 hour plasma concentration versus time data using non-compartmental methods. Pre-dose concentrations and concentrations prior to the first quantifiable concentration that were below the lower limit of quantitation were treated as missing.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose on Days 49 and 77
Population: All participants who received the study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ortho Tri-Cyclen | Time of Maximum Observed Plasma Concentration of Norgestrel | 1.8 hours |
| Ortho Tri-Cyclen + Daclatasvir | Time of Maximum Observed Plasma Concentration of Norgestrel | 2.0 hours |