None listed
Conditions
Brief summary
This is a first-in-human, Phase 1 study to evaluate the safety, tolerability, and pharmacokinetics of escalating, single and multiple oral doses of GS-1701 administered in healthy participants. This part of the study will assess drug-drug-interactions.
Interventions
This part of the study will proceed with two cohorts, governed by reviews of safety, tolerability, and any available pharmacokinetic (PK) data as well as by applicable stopping rules by the Safety Review Team (SRT)/dose-escalation team. Dose selection for Part C – Cohorts 8 and 9 will be based on safety and any available PK data from the SAD (Part A) and/or MAD (Part B) cohorts and may be initiated in parallel with other cohorts. The GS-1701 dose selected for Cohorts 8 & 9 will not exceed the hi
This part of the study will proceed with two cohorts, governed by reviews of safety, tolerability, and any available pharmacokinetic (PK) data as well as by applicable stopping rules by the Safety Review Team (SRT)/dose-escalation team. Dose selection for Part C – Cohorts 8 and 9 will be based on safety and any available PK data from the SAD (Part A) and/or MAD (Part B) cohorts and may be initiated in parallel with other cohorts. The GS-1701 dose selected for Cohorts 8 & 9 will not exceed the highest single dose already evaluated and deemed safe and tolerable in the SAD (Part A) portion of the study. Study drug adherence to be monitored by the Investigator. Part C (Drug-Drug-Interaction [DDI]) - Cohort 8 – Day 1, 7 and 16: single dose of 2.5 mg of oral midazolam (MDZ) in the morning, fasted state; Day 3-16: up to 1000 mg once daily of GS-1701 in the morning, orally, fasted state or up to 1000 mg of GS-1701 twice daily, in the morning and evening, orally, both fasted state. When oral MDZ and oral GS-1701 morning doses occur on the same day, doses are given simultaneously. - Cohort 9 - Day 1: single dose of up to 1000 mg of GS-1701 in the morning, orally, fasted state; Day 7: single dose of 40 mg of oral famotidine (FAM) in the morning, fasted state, followed by a single dose of up to 1000 mg of GS-1701 administered 2 hours after FAM, orally, fasted state. Strategies to monitor adherence will be determined by the Investigator and site processes. Part C (Cohort 8-9) is open-label, and participants will not be randomized. In Part C (Cohort 8), study drug will be administered in the morning (if once daily) or in the morning and evening (if twice daily). All morning doses will be administered following an overnight fast (no food or drink, except water, for at least 10 hours). In Part C (Cohort 9), study drug will be administered with 240 mL of water following an overnight fast (no food or drink, except water, for at least 10 hours).
Sponsors
Gilead Sciences, Inc.
Study design
Allocation
Non-randomised trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
• Participants assigned male or female at birth, aged 18 years through 45 years inclusive, and able to comply with treatment and follow-up. • Be a nonsmoker. The use of nicotine or nicotine-containing products must be discontinued greater than or equal to 90 days prior to the first dose of study drug. • Must, in the opinion of the investigator, be in good health based on medical history and physical examination, including vital signs. • Have a calculated body mass index (BMI) of greater than or equal to 19.0 and less than or equal to 30.0 kg/m2 at screening and at admission. • Negative serum pregnancy test at screening and at admission. • Have an estimated glomerular filtration rate (eGFR) calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation of greater than or equal to 90 mL/minute/1.73m2 at screening and at admission.
Exclusion criteria
• Breastfeeding or lactating participant • Have a history of any of the following: o Significant serious skin disease, such as but not limited to rash, eczema, psoriasis, or urticaria. o Significant drug sensitivity or drug allergy (such as but not limited to anaphylaxis or drug-induced liver injury). o Known hypersensitivity to the study drugs, their metabolites, or to formulation excipients for all cohorts. Known cherry allergy for participants in Cohort 8. o Significant cardiac disease (including history of myocardial infarction based on ECG and/or clinical history, any history of ventricular tachycardia, congestive heart failure, or dilated cardiomyopathy with left ventricular ejection fraction less than or equal to 40%); or a family history of long QT syndrome, or unexplained death in an otherwise healthy individual between the ages of 1 and 30 years. o Syncope, palpitations, or unexplained dizziness. o Implanted defibrillator or pacemaker. o Liver disease, including Gilbert syndrome. o Severe peptic ulcer disease, gastroesophageal reflux disease, or other gastric acid hypersecretory conditions requiring prolonged (greater than or equal to 6 months) medical treatment. o Medical or surgical treatment that permanently altered gastric absorption (eg, gastric or intestinal surgery). A history of cholecystectomy is not exclusionary. • Have any serious or active medical or psychiatric illness (including depression) that, in the opinion of the investigator, would interfere with participant treatment, assessment, or compliance with the protocol. This would include renal, cardiac, hematological, hepatic, pulmonary (including chronic asthma), endocrine (including diabetes), central nervous, gastrointestinal (including an ulcer), vascular, metabolic (thyroid disorders, adrenal disease), immunodeficiency disorders, active infection, or malignancy that are clinically significant or requiring treatment. • Have a hemoglobin value less than 11.5 g/dL for females or less than 13.0 g/dL for males at screening. • Have a reticulocyte count less than 20 x 109/L at screening.
Outcome results
None listed