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

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ClinicalTrials.gov Identifier: NCT02533427
Recruitment Status : Completed
First Posted : August 26, 2015
Last Update Posted : February 12, 2019
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Brief Summary:
This study will evaluate the effect of sofosbuvir (SOF)/velpatasvir (VEL)/GS-9857 fixed-dose combination (FDC) + GS-9857 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/GS-9857+GS-9857.

Condition or disease Intervention/treatment Phase
HCV Infection Drug: SOF/VEL/GS-9857 Drug: GS-9857 Drug: Norgestimate/ethinyl estradiol Phase 1

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


Arm Intervention/treatment
Experimental: SOF/VEL/GS-9857+GS-9857

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/GS-9857 FDC plus GS-9857.

Drug: SOF/VEL/GS-9857
SOF/VEL/GS-9857 (400/100/100 mg) FDC tablet administered orally once daily

Drug: GS-9857
GS-9857 100 mg tablet administered orally once daily

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 Name: Ortho-Tri-Cyclen® Lo




Primary Outcome Measures :
  1. PK parameter: AUCtau for norgestimate (if possible), norelgestromin, norgestrel, and ethinyl estradiol [ Time Frame: Predose and 0.25, 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.

  2. PK parameter: Ctau for norgestimate (if possible), norelgestromin, norgestrel, and ethinyl estradiol [ Time Frame: Predose and 0.25, 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.

  3. PK parameter: Cmax of norgestimate (if possible), norelgestromin, norgestrel, and ethinyl estradiol [ Time Frame: Predose and 0.25, 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 observed plasma concentration of drug.


Secondary Outcome Measures :
  1. Incidence of adverse events [ Time Frame: Up to 84 days ]
  2. Incidence of laboratory abnormalities [ Time Frame: Up to 84 days ]
    The percentage of participants experiencing any clinically significant laboratory abnormality will be summarized.

  3. PK parameter: Tmax of norgestimate (if possible), norelgestromin, norgestrel, ethinyl estradiol, SOF (and its metabolites GS-566500 and GS-331007), VEL, and GS-9857 (and its metabolites if appropriate) [ Time Frame: Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours postdose ]
    Tmax is defined as the time (observed time point) of Cmax.

  4. PK parameter: Tlast of norgestimate (if possible), norelgestromin, norgestrel, ethinyl estradiol, SOF (and its metabolites GS-566500 and GS-331007), VEL, and GS-9857 (and its metabolites if appropriate) [ Time Frame: Predose and 0.25, 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 (last observed quantifiable plasma concentration of the drug).

  5. PK parameter: λz for norgestimate (if possible), norelgestromin, norgestrel, ethinyl estradiol, SOF (and its metabolites GS-566500 and GS-331007), VEL, and GS-9857 (and its metabolites if appropriate) [ Time Frame: Predose and 0.25, 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.

  6. PK parameter: CLss/F for norgestimate (if possible), norelgestromin, norgestrel, ethinyl estradiol, SOF (and its metabolites GS-566500 and GS-331007), VEL, and GS-9857 (and its metabolites if appropriate) [ Time Frame: Predose and 0.25, 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 oral steady-state clearance after administration of the drug.

  7. PK parameter: t1/2 of norgestimate (if possible), norelgestromin, norgestrel, ethinyl estradiol, SOF (and its metabolites GS-566500 and GS-331007), VEL, and GS-9857 (and its metabolites if appropriate) [ Time Frame: Predose and 0.25, 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 in plasma.

  8. PK parameter: Cmax of SOF (and its metabolites GS-566500 and GS-331007), VEL, and GS-9857 (and its metabolites if appropriate) [ Time Frame: Predose and 0.25, 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 observed plasma concentration of drug.

  9. PK parameter: Ctau for SOF (and its metabolites GS-566500 and GS-331007), VEL, and GS-9857 (and its metabolites if appropriate) [ Time Frame: Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours postdose ]
    Ctau is defined as the observed drug concentration at the end of the dosing interval.

  10. PK parameter: AUCtau for SOF (and its metabolites GS-566500 and GS-331007), VEL, and GS-9857 (and its metabolites if appropriate) [ Time Frame: Predose and 0.25, 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.



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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Premenopausal female
  • Must have a calculated 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02533427


Locations
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New Zealand
Christchurch, New Zealand
Sponsors and Collaborators
Gilead Sciences
Investigators
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Study Director: Luisa Stamm, MD, PhD Gilead Sciences

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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02533427     History of Changes
Other Study ID Numbers: GS-US-367-1909
First Posted: August 26, 2015    Key Record Dates
Last Update Posted: February 12, 2019
Last Verified: April 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at https://www.gilead.com/about/ethics-and-code-of-conduct/policies.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: 18 months after study completion
Access Criteria: A secured external environment with username, password, and RSA code.
URL: https://www.gilead.com/about/ethics-and-code-of-conduct/policies
Additional relevant MeSH terms:
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Estradiol 3-benzoate
Estradiol 17 beta-cypionate
Estradiol
Polyestradiol phosphate
Ethinyl Estradiol
Sofosbuvir
Velpatasvir
Contraceptive Agents
Norgestimate
Norgestrel
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Reproductive Control Agents
Contraceptive Agents, Female
Antiviral Agents
Anti-Infective Agents
Contraceptives, Oral, Synthetic
Contraceptives, Oral