A Phase 1 Study to Evaluate the Pharmacokinetics, Metabolism, and Excretion of GS-5806

This is a single center, open-label, Phase 1 study to determine the mass balance of of GS-5806 following administration of a single, oral dose of radiolabeled [14C]-GS-5806 in healthy subjects.

Study Overview

• Status: Completed
• Conditions: RSV Infection
• Intervention / Treatment: Drug: GS-5806

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53704
      • Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Have a calculated body mass index (BMI) from 19 to 30 kg/m2 at study screening.
• In the opinion of the Investigator, subjects must be in good health based upon medical history, physical examination (including vital signs), and screening and baseline laboratory evaluations (hematology, chemistry, and urinalysis must fall within the normal range of the local laboratory's reference ranges unless the results have been determined by the Investigator to have no clinical significance).
• Agree to utilize a highly effective method of contraception during heterosexual intercourse from baseline throughout the study period and for 90 days following discontinuation of study drug.
• Refrain from sperm donation from Day -1 through completion of the study and continuing for at least 90 days from the date of last dose of study drug.
• Have a creatinine clearance (CLcr) > 80 mL/min (using the Cockcroft-Gault method) based on serum creatinine and actual body weight as measured at the screening evaluation.
• Anticipated, regular, average bowel movement of 1-2 per day.

Exclusion Criteria:

• Smokers, use of nicotine or nicotine-containing products within 90 days prior to the first dose of study drug. Smokers will be defined as any subject who reports tobacco use and/or who has a urine cotinine ≥200 ng/mL at screening.
• A positive HIV-1 antibody, Hepatitis B surface antigen (HBsAg), or Hepatitis C antibody test result.
• Have any serious or active medical or psychiatric illness which, in the opinion of the Investigator, would interfere with subject treatment, assessment, or compliance with the protocol.
• Have previously participated in an investigational trial involving administration of any investigational compound within 30 days prior to study dosing.
• Have participated in studies using radiomaterials or ionizing radiations or have been otherwise exposed to significant diagnostic (excluding dental X-rays), therapeutic, or occupational radiation.
• Current alcohol or substance abuse as judged by the Investigator or as determined by a positive alcohol or drug test at screening or baseline visit.
• Have poor venous access and are unable to donate blood.
• Have donated blood within 56 days of study dosing or plasma within 7 days of study dosing.
• Have been vaccinated within 90 days of study dosing or, for the influenza vaccine, within 14 days prior to study dosing.
• Have taken any prescription medications or over-the-counter medications, including herbal products, or medications that affect gastric pH (ie, antacids, H2RAs, and/or proton pump inhibitors) within 28 days of commencing study drug dosing with the exception of vitamins, acetaminophen, and ibuprofen.
• Have taken any systemic steroids, immunosuppressant therapies or chemotherapeutic agents within 3 months of study screening, or expected to receive these agents during the study (eg, corticosteroids, immunoglobulins, and other immune- or cytokine-based therapies).

• Evidence of any of the following:

  1. Clinically significant ECG abnormalities.
  2. Syncope, palpitations, or unexplained dizziness.
  3. Liver disease (including known Gilbert's Disease) or clinical evidence of liver injury or hepatic synthetic dysfunction.
  4. Severe peptic ulcer disease, gastroesophageal reflux disease, or other gastric acid hypersecretory conditions requiring prolonged (>6 months) medical treatment.
  5. History of medical or surgical treatment that permanently alters the gastric conditions (eg, gastrectomy).
  6. Significant drug sensitivity or drug allergy.
  7. Known hypersensitivity to sulfa drugs.
  8. Known hypersensitivity to the study drug, metabolites or formulation excipients.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention Arm; One-time single dose of 50 mg radiolabeled GS-5806 administered orally in 3 capsules in the morning.	Drug: GS-5806

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urine and fecal recovery of total [14C]-radioactivity	The primary outcome measure of this study is the urine and fecal recovery of total [14C]-radioactivity.	22 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recovery of [14C]-GS-5806	The secondary endpoint measure is the urine and fecal recovery of [14C]-GS-5806 and, where measurable, its metabolite(s).	22 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma and blood concentration and PK parameters - Radioactivity	Secondary endpoint measures include the plasma and blood concentration and PK parameters of total [14C]-radioactivity, and the plasma to blood ratio of [14C]-radioactivity.	22 days
Plasma and blood concentration and PK parameters - Non-radiolabeled	Secondary endpoint measures include the plasma concentration and PK parameters of non-radiolabeled GS-5806 and, where measurable, its metabolite(s).	22 Days
Plasma and blood concentration and PK parameters - [14C]-GS-5806	Secondary endpoint measures include the plasma concentration and PK parameters of [14C]-GS-5806, and where measurable, its metabolite(s).	22 Days

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Director: Seth Toback, M.D., Gilead Sciences

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: February 26, 2013
• First Submitted That Met QC Criteria: February 26, 2013
• First Posted (Estimate): February 28, 2013

Study Record Updates

• Last Update Posted (Estimate): June 10, 2013
• Last Update Submitted That Met QC Criteria: June 6, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Keywords: RSV infection
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Paramyxoviridae Infections; Mononegavirales Infections; Pneumovirus Infections; Respiratory Syncytial Virus Infections
• Other Study ID Numbers: GS-US-218-0109