GSK1349572 Exposure in Blood, Seminal Fluid, and Rectal Fluid and Tissue in Healthy Male Subjects

NCT01459315 | Completed Phase 1

• 1 other identifier: 11-1733
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to describe drug concentrations in blood plasma, rectal fluid, rectal tissue, and seminal fluid in HIV negative men following single and multiple doses of an investigational HIV medication known as GSK1349572 (dolutegravir).

Conditions

Healthy

Keywords

Healthy; Male; GSK1349572; Dolutegravir; DTG; Integrase; HIV

Outcome Measures

Primary Outcomes (19)

• Area under the concentration versus time curve (AUC) in blood plasma after a single dose

  The area under the concentration time curve will be determined from all sample collection time points over a 24 hour period. Sample collection for blood plasma will occur pre-dose, then 1, 2, 3, 4, 5, 6, 8, 12, 18, and 24 hours post-dose. AUCs will be determined for individual subjects and for all subjects combined following a single dose.

  24 hours

• Peak concentration (Cmax) in blood plasma after a single dose

  Peak drug concentration in blood plasma after the first dose will be determined from samples taken pre-dose, then at 1, 2, 3, 4, 5, 6, 8, 12, 18, and 24 hours post-dose in each subject and across all subjects.

  24 hours

• Area under the concentration versus time curve (AUC) in blood plasma at steady state

  The area under the concentration time curve will be determined from all sample collection time points over a 24 hour period. Sample collection for blood plasma will occur pre-dose, then 1, 2, 3, 4, 5, 6, 8, 12, 18, and 24 hours post-dose. AUCs will be determined for individual subjects and for all subjects combined at steady state.

  24 hours

• Peak concentration (Cmax) in blood plasma at steady state

  Peak drug concentration in blood plasma at steady state will be determined from samples taken pre-dose, then at 1, 2, 3, 4, 5, 6, 8, 12, 18, and 24 hours post-dose in each subject and across all subjects.

  24 hours

• Area under the concentration versus time curve (AUC) in seminal fluid after a single dose

  The area under the concentration time curve after a single dose will be determined from all sample collection time points over a 24 hour period for seminal fluid. Sample collection will occur pre-dose and at two time points per subject 1, 3, 6, 12, 18, or 24 hours post-dose. AUCs will be determined for all subjects combined.

  24 hours

• Peak drug concentration (Cmax) in seminal fluid after a single dose

  Peak drug concentration in seminal fluid will be determined from samples taken pre-dose, then at 2 time points per subject 1, 3, 6, 12, 18, or 24 hours post-dose. Cmax will be determined for all subjects combined.

  24 hours

• Area under the concentration versus time curve (AUC) for seminal fluid at steady state

  The area under the concentration time curve at steady state for seminal fluid will be determined from all sample collection time points over a 48 hour period for seminal fluid. Sample collection will occur at 1, 3, 6, 12, 18, or 24 hours post-dose over 48 hours with 3 collections per subject in each 24 hour period. AUCs will be determined for each subject and across all subjects.

  48 hours

• Peak drug concentration (Cmax) for seminal fluid at steady state

  Peak drug concentration (Cmax) at steady state for seminal fluid will be determined from all sample collection time points over a 48 hour period. Sample collection will occur at 1, 3, 6, 12, 18, or 24 hours post-dose over 48 hours with 3 collections per subject in each 24 hour period. Cmax will be determined for each subject and across all subjects.

  24 hours

• Area under the concentration versus time curve (AUC) for rectal fluid after a single dose

  The area under the concentration time curve after a single dose will be determined from all sample collection time points over a 24 hour period for rectal fluid. Sample collection will occur pre-dose and at two time points per subject 1, 3, 6, 12, 18, or 24 hours post-dose. AUCs will be determined for all subjects combined.

  24 hours

• Peak drug concentration (Cmax) in rectal fluid after a single dose

  Peak drug concentration in rectal fluid will be determined from samples taken pre-dose, then at 2 time points per subject 1, 3, 6, 12, 18, or 24 hours post-dose. Cmax will be determined for all subjects combined.

  24 hours

• Area under the concentration versus time curve (AUC) for rectal fluid at steady state

  The area under the concentration time curve at steady state for rectal fluid will be determined from all sample collection time points over a 48 hour period. Sample collection will occur at 1, 3, 6, 12, 18, or 24 hours post-dose over 48 hours with 3 collections per subject in each 24 hour period. AUCs will be determined for each subject and across all subjects.

  48 hours

• Peak drug concentration (Cmax) for rectal fluid at steady state

  Peak drug concentration (Cmax) at steady state for rectal fluid will be determined from all sample collection time points over a 48 hour period. Sample collection will occur at 1, 3, 6, 12, 18, or 24 hours post-dose over 48 hours with 3 collections per subject in each 24 hour period. Cmax will be determined for each subject and across all subjects.

  48 hours

• Area under the concentration versus time curve (AUC) for rectal tissue after a single dose

  The area under the concentration time curve for rectal tissue after a single dose will be determined from all sample collection time points over a 24 hour period. One sample collection will be performed per subject at either 1, 3, 6, 12, 18, or 24 hours post-dose and AUC will be determined for all subjects combined.

  24 hours

• Peak drug concentration (Cmax) for rectal tissue after a single dose

  Peak drug concentration in rectal tissue after a single dose will be determined from all sample collection time points over a 24 hour period. One sample collection will be performed per subject at either 1, 3, 6, 12, 18, or 24 hours post-dose and Cmax will be determined for all subjects combined.

  24 hours

• Area under the concentration versus time curve (AUC) for rectal tissue at steady state

  The area under the concentration time curve for rectal tissue at steady state will be determined from all sample collection time points over a 24 hour period. One sample collection will be performed per subject at either 1, 3, 6, 12, 18, or 24 hours post-dose and AUC will be determined for all subjects combined.

  24 hours

• Peak drug concentration (Cmax) for rectal tissue at steady state

  Peak drug concentration in rectal tissue at steady state will be determined from all sample collection time points over a 24 hour period. One sample collection will be performed per subject at either 1, 3, 6, 12, 18, or 24 hours post-dose and Cmax will be determined for all subjects combined.

  24 hours

• Area under the concentration versus time curve ratios after a single dose

  AUC ratios will be determined to compare blood plasma concentrations after a single dose with concentrations in rectal tissue, rectal fluid, and seminal fluid.

  24 hours

• Area under the concentration time curve ratios at steady state

  AUC ratios will be determined to compare blood plasma concentrations at steady state with concentrations in rectal tissue, rectal fluid, and seminal fluid.

  24 hours

• Accumulation ratio

  Area under the concentration time curve (AUC) in each matrix at steady state will be compared to AUC after a single dose to determine accumulation ratios.

  24

Study Arms (1)

GSK1349572

EXPERIMENTAL

Drug: dolutegravir

Interventions

dolutegravir DRUG

Subjects will take a GSK1349572 (dolutegravir) 50mg tablet by mouth once daily for 8 days. GSK1349572 concentrations will be measured in blood plasma, seminal fluid, rectal fluid, and rectal tissue over 24 hours after a single dose and over two 24 hour periods once steady state is reached. Blood plasma will be collected pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, 18, and 24 hours after dosing. Each subject will also provide a total of 9 seminal and rectal fluid samples and have 2 rectal tissue biopsies performed pre-dose or at 1, 3, 6, 12, 18, or 24 hours after receiving single or multiple doses.

Also known as: GSK1349572, DTG

GSK1349572

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male subjects between the ages of 18 and 49 years, inclusive, with intact genital tract and gastrointestinal tract.
• Body Mass Index (BMI) of 18 to 30 kg/m2; and a total body weight greater than 50 kg (110 lbs).
• Evidence of a personally signed and dated informed consent document
• Willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other trial procedures.

You may not qualify if:

• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease
• Subjects with a history of gastrectomy, colostomy, ileostomy, or any other procedure altering the gastrointestinal tract.
• Subjects with a history of vasectomy, prostatectomy, or any other procedure altering the male reproductive tract.
• Subjects with inflammatory bowel diseases (ulcerative colitis or Crohn's disease), irritable bowel syndrome, or other abnormalities of the colorectal mucosa, or significant colorectal symptom(s)
• Subject who is unwilling to refrain from any sexual activity for 72 hours before study visit Day 0 and until discharge from the study.
• Subject who is unwilling to refrain from rectal insertion of medical/recreation devices and products and from receptive anal intercourse, for 72 hours before study visit Day 0 and through 7 days after the last biopsy.
• History of febrile illness within 14 days prior to the first dose.
• Any condition possibly affecting drug absorption (eg, gastrectomy).
• A positive urine drug screen.
• A positive result for HIV, Hepatitis B surface antigen or Hepatitis B core antibody screening tests or anti-hepatitis C virus serology
• A positive test for syphilis, rectal gonorrhea, chlamydia, or HSV-2 (active lesions) at screening.
• Current alcohol consumption exceeding 14 drinks \[1 drink = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of spirits\] per week or unwilling to abstain from alcohol use from 48 hours prior to the first dose of study medication until after the follow-up visit.
• History of regular use of tobacco- or nicotine-containing products exceeding an equivalent of 5 cigarettes per day within three months prior to screening or unwilling to abstain from cigarette smoking completely during visits.
• Treatment with an investigational drug within 4 months preceding the first dose of trial medication.
• Participated in a rectal biopsy study in the 12 months preceding the first dose of trial medication.

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

University of North Carolina, Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

MeSH Terms

Interventions

dolutegravir

Study Officials

• Kristine B Patterson, MD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

• Benjamin N Greener, PharmD

  University of North Carolina, Chapel Hill

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: October 21, 2011
• First Posted: October 25, 2011
• Study Start: November 1, 2011
• Primary Completion: November 1, 2012
• Study Completion: December 1, 2012
• Last Updated: July 4, 2013

Record last verified: 2013-07

Locations

US (1)