Comparison of Concentration-time Course of Plasma and Intracellular Raltegravir in Healthy Volunteers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01027182
Recruitment Status : Completed
First Posted : December 7, 2009
Last Update Posted : March 19, 2010
National University Hospital, Singapore
Merck Sharp & Dohme Corp.
Information provided by:
Changi General Hospital

Brief Summary:
The investigators hypothesize that the concentration-time profile of raltegravir is different in cells than that in plasma. Intracellular raltegravir concentrations may be higher and its half-life longer than in plasma. This may explain the efficacy of raltegravir despite variable plasma concentrations.

Condition or disease Intervention/treatment Phase
Human Immunodeficiency Virus Drug: Raltegravir Phase 1

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Official Title: Comparison of Concentration-time Course of Plasma and Intracellular Raltegravir in Healthy Volunteers.
Study Start Date : December 2009
Actual Primary Completion Date : March 2010
Actual Study Completion Date : March 2010

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
No Intervention: Raltegravir Drug: Raltegravir
One 400mg tablet on day 1.
Other Name: ISENTRESS, 400mg

Primary Outcome Measures :
  1. To determine the time course and half-life of intracellular raltegravir after a single dose, and compare with plasma concentrations. [ Time Frame: 3 months ]

Secondary Outcome Measures :
  1. To develop analytical methods to measure intracellular raltegravir using liquid chromatography / mass spectrometry (LCMS). [ Time Frame: 3 months ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   21 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • Body Mass Index (BMI) of 18 to 30 kg/m2, inclusive. BMI = weight (kg)/ [height (m)]2 and weigh at least 50kg.
  • Non-smoking or smoking no more than 10 cigarettes, or 2 cigars, or 2 pipes per day for at least 3 months prior to selection.
  • Women of childbearing potential (WOCBP) must not be nursing or pregnant.
  • Women of childbearing potential (have not been postmenopausal for at least 2 years nor undergone total hysterectomy) must have a negative serum Beta-HCG test performed at screening.
  • Female subjects who are not of reproductive potential (have been postmenopausal for at least 2 years or undergone total hysterectomy) or whose male partner has undergone successful vasectomy with resultant azoospermia or has azoospermia for any other reason, are eligible without requiring the use of contraception. Documentation of menopause, sterilization (total hysterectomy or vasectomy) and azoospermia must be provided to study personnel at time of screening.
  • Both male and female study volunteers of reproductive potential must agree not to participate in a conception process (i.e., active attempt to become pregnant or to impregnate via sperm donation or in vitro fertilization), and if participating in sexual activity that could lead to pregnancy, the female study volunteer/male partner must use a form of contraception as specified below while receiving protocol-specified medication(s) and for 7 days after stopping the medication(s). Male study volunteers will be required to use a barrier method for at least 7 days after completion of the study.

Exclusion Criteria:

  • History or current evidence of any significant acute or chronic medical illness that, within the investigator's discretion, would interfere with the conduct or interpretation of the study.
  • Proven or suspected acute hepatitis at the time of study entry.
  • Current or recent (within 3 months) gastrointestinal disease which would interfere with the conduct or interpretation of the study.
  • Any major surgery within 8 weeks of enrollment. Any gastrointestinal surgery that could impact upon the absorption of study drug.
  • Donation of blood or plasma within 60 days of screening.
  • Inability to tolerate oral medication.
  • Inability to tolerate venepuncture and/or absence of secure venous access.
  • Inability to give informed consent voluntarily before the first trial-related activity.
  • Known or suspected HIV infection or chronic HBV or HCV infection
  • Known active drug or alcohol abuse, which in the opinion of the investigator makes study participation to completion unlikely.
  • Any other significant medical, psychiatric and/or social issue as determined by the Investigator that would compromise subject's safety and/or compliance with trial procedures.
  • Subjects with AST, ALT or total bilirubin above the upper limit of normal.
  • Haemoglobin < 10.9 g/dL, and platelet count < 125,000/mm3.
  • Creatinine clearance <60 ml/min
  • Lipase or pancreatic amylase >1.1x ULN
  • Fasting triglyceride >300 mg/dL.
  • Absolute Neutrophil Count (ANC) <1300/mm3
  • Serum creatinine grade 1 or greater (≥ 1.1 x upper limit of laboratory normal range [ULN])
  • Any other clinically significant screening lab abnormality (as determined by the investigator)
  • Exposure to any investigational drug (excluding raltegravir) within 90 days of enrollment and throughout the study.
  • Any previous clinically significant allergy or hypersensitivity or intolerance to raltegravir or any other ingredient of the tablets.
  • Use of any agent, within 2 weeks of dosing, that is known to induce or inhibit drug metabolizing enzymes.
  • Use of concomitant medication, including investigational, prescription, and any over-the-counter drugs and dietary supplements with the following exceptions, aspirin, acetaminophen, chlorpheniramine, daily multivitamins, mineral supplements and hormonal oral contraceptives. Concomitant medication other than those listed above must have been discontinued within 14 days of study entry.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01027182

Changi General Hospital
Singapore, Singapore, 529889
Sponsors and Collaborators
Changi General Hospital
National University Hospital, Singapore
Merck Sharp & Dohme Corp.
Principal Investigator: Edmund JD Lee, Professor Changi General Hospital

Wenning, L. A., E. Hwang, et al. (2008). Pharmacokinetic/Pharmacodynamic (PK/PD) Analyses for Raltegravir (RAL) in Phase III Studies in Treatment Experienced HIV- Infected Patients Following 48 Weeks of Treatment. ICAAC. Washington DC, USA
Merck &Co Inc. (2007). Isentress (raltegravir) tablets. FDA approved label.

Responsible Party: Professor Edmund Lee, Changi General Hospital Identifier: NCT01027182     History of Changes
Other Study ID Numbers: RAL
First Posted: December 7, 2009    Key Record Dates
Last Update Posted: March 19, 2010
Last Verified: March 2010

Keywords provided by Changi General Hospital:

Additional relevant MeSH terms:
Immunologic Deficiency Syndromes
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Raltegravir Potassium
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
HIV Integrase Inhibitors
Integrase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action