Clinical trial NCT06310616: A Study to Investigate the Potential Drug-Drug Interaction Between VH4524184 and Oral Contraceptive (Loestrin) in Healthy Adult Female Participants
Official title: A Phase 1, Single-center, Open-label Study to Evaluate the Pharmacokinetics of Oral Contraceptive Containing Norethindrone and Ethinyl Estradiol (Loestrin) When Co-administered With VH4524184 in Healthy Adult Female Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Keywords: HIV
Oral contraceptive
Pharmacokinetic
Ethinyl estradiol
Norethindrone acetate
Potential drug-drug interaction
Healthy adult female participants
Lead sponsor: ViiV Healthcare
Sponsor class: INDUSTRY
First posted: 2024-03-15
Enrollment: 26
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This study aims to assess any impact of VH4524184 on the pharmacokinetic (PK) profile of an ethinyl estradiol (EE) and norethindrone acetate (NEA) containing oral contraceptive (OC) administered to healthy adult female participants.


Eligibility criteria: Inclusion Criteria:

* Healthy participants 18 to 45 years of age
* POCBP with intact ovarian function by medical history and history of regular menstrual cycles for the past 12
* Body weight greater than or equal to (≥) 45 kilograms (kg) and Body mass index (BMI) within the range of 18.5 to 32.0 kg/m2
* Female participants of childbearing potential must use approved highly effective non-hormonal forms of birth control.
* Capable of giving signed informed consent.

Exclusion Criteria:

* History or presence of clinical condition or disorder that could be capable of significantly altering the absorption, metabolism, or elimination of drugs.
* Lymphoma, leukemia, or any malignancy within the past 5 years with some exceptions
* Breast cancer or in remission within the past 10 years.
* Current or chronic history of liver disease or known hepatic or biliary abnormalities with some exceptions.
* Any personal and/or family history of thrombophilia or blood clots
* Medical history of cardiac arrhythmias or cardiac disease or a family and personal history of long QT syndrome.
* History of seizure(s).
* Any known or suspected pre-existing psychiatric condition, including depression, anxiety, and/or insomnia/sleep disturbances.
* Subjects with history of drug hypersensitivity, delayed-type hypersensitivity, or severe hypersensitivity reactions, as well as history of sensitivity to the study interventions will be excluded.
* Participant is mentally or legally incapacitated.

Prior/Concomitant Therapy

• Any warnings and contraindications that apply based on Loestrin prescribing information.

Prior/Concurrent Clinical Study Experience

* Exposure to more than 4 new investigational products (including long-acting investigational products) within 12 months prior to the first dosing day.
* Current enrollment or past participation in another investigational study in which an investigational intervention was administered within the last 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer) before signing of consent (or screening) any other clinical study.
* Participant has donated or lost blood (\>500 millilitres (mL)) or blood products within 2 months (56-day period) prior to Day -1 admission or has donated plasma within 30 days prior to first OC administration.
* Current enrollment or past participation in this clinical study. Unwillingness or inability to follow the procedures outlined in the protocol.
* Positive Human immunodeficiency virus 1 (HIV-1) antibody test.
* Pregnant at screening) or lactating.
* POCBP who are unwilling or unable to use an appropriate non-hormonal method of highly effective contraception from at least Day 1 of Treatment Period 1 until 14 days after the last dose of VH4524184.
* Regular alcohol consumption within 6 months prior to the study defined as an average weekly intake of \>7 units for females. One unit is equivalent to 8 grams (g) of alcohol: a half-pint (\~240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
* Regular use of known drugs of abuse.

Primary outcomes:
measure: Area under the concentration-time curve (AUC) from time zero (pre-dose) to the end of the dosing interval at steady state (AUC0-Tau, ss) of EE and NEA without coadministration with VH4524184
timeFrame: On Day 10
measure: AUC0-Tau, ss of EE and NEA with coadministration with VH4524184
timeFrame: On Day 20
measure: Maximum plasma concentration (Cmax) for EE and NEA without coadministration with VH4524184
timeFrame: On Day 10
measure: Cmax for EE and NEA with coadministration with VH4524184
timeFrame: On Day 20
Secondary outcomes:
measure: Number of participants with adverse events (AEs) and severity of AEs
timeFrame: From Day -28 (Run-In-Period) up to approximately 2 months (Day 28 +/- 3 days)
measure: Number of participants with AEs leading to discontinuation of study intervention
timeFrame: Throughout the study treatment period (from Day -28 up to Day 20)
measure: Change from baseline of liver panel laboratory parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ASP) (International units per liter)
timeFrame: Baseline (Day -28) up to Day 21
measure: Change from baseline of liver panel laboratory parameters: Total bilirubin, Direct bilirubin (Micromoles per liter [umol/L])
timeFrame: Baseline (Day -28) up to Day 21
measure: Change from baseline of liver panel laboratory parameters: International normalized ratio (INR) (Ratio)
timeFrame: Baseline (Day -28) up to Day 21
measure: Number of participants with maximum toxicity grade increase from baseline of liver panel laboratory parameters: ALT, AST, alkaline phosphatase, total bilirubin, Direct bilirubin, and INR
timeFrame: Baseline (Day -28) up to Day 21
measure: Maximum plasma concentration at steady state (Cmax,ss) for VH4524184
timeFrame: On Day 20
measure: Time to maximum concentration at steady state (Tmax, ss) during dosing interval for VH4524184
timeFrame: On Day 20
measure: Area under the concentration-time curve from time zero(pre-dose) to the end of the dosing interval at steady state (AUC0-Tau, ss) for VH4524184
timeFrame: On Day 20
measure: Trough concentration prior to the next dose (Ctrough) for VH4524184
timeFrame: On Day 12, Day 16, and Day 20
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: GSK Investigational Site
state: Texas
Study officials:
References: