Drug-Drug Interaction Study of Vesatolimod in Adults With HIV-1 Who Have Very Low or Undetectable Virus Levels
Study Details
Study Description
Brief Summary
The primary objectives of this study are to evaluate the impact of cobicistat (COBI) (P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and strong cytochrome P450 enzyme [CYP]3A inhibitor), voriconazole (VOR) (strong CYP3A inhibitor), and rifabutin (RFB) (moderate CYP3A inducer) on vesatolimod (VES) pharmacokinetics (PK) and to evaluate safety in virologically suppressed adults with HIV-1 on antiretroviral therapy (ART).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Vesatolimod (VES) + Cobicistat (COBI) + Voriconazole (VOR) Participants will receive: In Period 1 (duration 1 day): a single dose of VES 2 mg on Day 1 In Period 2 (duration 5 days): COBI 150 mg once daily on Days 1 to 5; a single dose of VES 2 mg will be coadministered on Day 2 In Period 3 (duration 6 days): a loading dose of VOR 400 mg twice daily on Day 1, then VOR 200 mg twice daily on Days 2 to 6; a single dose of VES 2 mg will be coadministered in the morning on Day 3 There will be a washout period of 7 to 14 days between VES doses in Periods 1 and 2 and a washout period of 14 to 21 days between VES doses in Periods 2 and 3. Participants should inform the site of any adverse event (AE) during the washout period. |
Drug: Vesatolimod
Administered orally
Other Names:
Drug: Cobicistat
Administered orally
Other Names:
Drug: Voriconazole
Administered orally
Other Names:
|
| Experimental: Vesatolimod (VES) + Rifabutin (RFB) Participants will receive: In Period 1 (duration 1 day): participants will receive a single dose of VES 6 mg on Day 1 In Period 2 (duration 9 days): participants will receive RFB 300 mg once daily on Days 1 to 9; a single dose of VES 6 mg will be coadministered on Day 6 There will be a washout period of 7 to 14 days between VES doses in Periods 1 and 2. Participants should inform the site of any AE during the washout period. |
Drug: Vesatolimod
Administered orally
Other Names:
Drug: Rifabutin
Administered orally
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Pharmacokinetic (PK) Parameter : AUClast of Vesatolimod (VES) [Predose up to 96 hours postdose]
AUClast is defined as an area under the concentration versus time curve from time zero to the last quantifiable concentration.
- PK Parameter : AUCinf of VES [Predose up to 96 hours postdose]
AUCinf is defined as an area under the concentration versus time curve extrapolated to infinite time, calculated as AUClast + (Clast/Lambda z).
- PK Parameter : Cmax of VES [Predose up to 96 hours postdose]
Cmax is defined as the maximum observed concentration of drug.
- PK Parameter : %AUCexp of VES [Predose up to 96 hours postdose]
%AUCexp is defined as the percentage of AUC extrapolated between AUClast and AUCinf.
- PK Parameter : Tmax of VES [Predose up to 96 hours postdose]
Tmax is defined as the time (observed time point) of Cmax.
- PK Parameter : Clast of VES [Predose up to 96 hours postdose]
Clast is defined as the last observed quantifiable concentration of the drug.
- PK Parameter : Tlast of VES [Predose up to 96 hours postdose]
Tlast is defined as the time (observed time point) of Clast.
- PK Parameter : Lambda z of VES [Predose up to 96 hours postdose]
Lambda z is defined as the terminal elimination rate constant, estimated by linear regression of the terminal elimination phase of the log concentration of drug versus time curve of the drug.
- PK Parameter : t1/2 of VES [Predose up to 96 hours postdose]
t1/2 is defined as the terminal elimination half-life.
- PK Parameter : CL/F of VES [Predose up to 96 hours postdose]
CL/F is defined as an apparent oral clearance.
- PK Parameter : Vz/F of VES [Predose up to 96 hours postdose]
Vz/F is defined as an apparent volume of distribution of the drug.
- Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) [First dose date up to Week 7 plus 30 days]
- Percentage of Participants Experiencing Treatment-Emergent Graded Laboratory Abnormalities [First dose date up to Week 7 plus 30 days]
Eligibility Criteria
Criteria
Key Inclusion Criteria:
-
On an antiretroviral therapy (ART) regimen for at least 6 consecutive months, with no change in the ART regimen within 2 months prior to screening. Permitted ARTs are as follows:
-
Cohort 1: bictegravir (BIC), dolutegravir (DTG), raltegravir (RAL), or doravirine (DORI) + nucleoside reverse transcriptase inhibitor (NRTIs)
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Cohort 2: DTG/abacavir (ABC)/lamivudine (3TC), DTG/3TC, or DTG + NRTIs
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Plasma HIV-1 RNA levels less than 50 copies/mL at screening
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Have normal hematologic function with an absolute neutrophil count greater than or equal to 1.5 × 109/L, platelets greater than or equal to 150 × 109/L; hemoglobin greater than or equal to 10.5 g/dL for females and greater than or equal to 11.5 g/dL for males
-
clusters of differentiation (CD)4 T cell count greater than or equal to 350 cells/μL
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Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 2.5 x upper limit of normal (ULN) and total bilirubin less than or equal to 1.5 mg/dL, or normal direct bilirubin and creatinine less than or equal to 1.25 x ULN.
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Have a calculated creatinine clearance (CLcr) of at least 60 mL/min (using the Cockcroft-Gault method) based on serum creatinine and actual body weight as measured at screening and upon admission
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Individuals assigned female at birth and of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception.
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Must be willing and able to comply with all study requirements and available to complete the study schedule of assessments.
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In the judgment of the investigator, be in good general health, based on review of the results from a screening visit
Key Exclusion Criteria:
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Have received any study drug within 30 days prior to study dosing
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Participation in any other clinical study (including observation studies) without prior approval from the sponsor is prohibited while participating in this study
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Have current alcohol or substance abuse judged by the investigator to potentially interfere with individual compliance or individual safety, or a positive drug or alcohol test at screening or baseline.
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Have a positive test result for hepatitis B virus (HBV) surface antigen (HBsAg), or hepatitis C virus (HCV) antibody at screening.
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Acute febrile illness within 35 days prior to Day 1
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Have been treated with systemic steroids, immunosuppressant therapies, or chemotherapeutic agents within 3 months prior to screening or is expected to receive these agents during the study
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Received any vaccine or immunomodulatory medication within 4 weeks prior to screening. Elective vaccination (eg, flu shot, hepatitis A or B vaccine) during the course of the study will require prior approval from the sponsor.
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COVID-19 vaccinations are allowed, with the requirement that they should not be administered within 7 ± 2 days of receiving VES
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Have a history of any of the following:
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Significant serious skin disease, such as but not limited to rash, food allergy, eczema, psoriasis, or urticaria.
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Significant drug sensitivity or drug allergy (such as anaphylaxis or hepatoxicity)
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Known hypersensitivity to the study drugs, their metabolites, or to formulation excipients
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Autoimmune disease
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Significant cardiac disease or a family history of long QT syndrome, or unexplained death in an otherwise healthy individual between the ages of 1 and 30 years.
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Syncope, palpitations, or unexplained dizziness
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Implanted defibrillator or pacemaker
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Liver disease, including Gilbert syndrome
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Severe peptic ulcer disease requiring prolonged (≥ 6 months) medical treatment
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Medical or surgical treatment that permanently altered gastric absorption (eg, gastric or intestinal surgery). A history of cholecystectomy is not exclusionary.
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Have any serious or active medical or psychiatric illness (including depression) that, in the opinion of the investigator, would interfere with individual treatment, assessment, or compliance with the protocol.
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For Cohort 1, individuals with CYP2C19 genotype of CYP2C19*2/2, CYP2C192/3, or CYP2C193/*3
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Contacts and Locations
Locations
No locations specified.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-382-1587