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

NCT01027182 | Completed Phase 1

• 1 other identifier: RAL
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

Human Immunodeficiency Virus

Keywords

HIV

Outcome Measures

Primary Outcomes (1)

• To determine the time course and half-life of intracellular raltegravir after a single dose, and compare with plasma concentrations.

  3 months

Secondary Outcomes (1)

• To develop analytical methods to measure intracellular raltegravir using liquid chromatography / mass spectrometry (LCMS).

  3 months

Study Arms (1)

Raltegravir

NO INTERVENTION

Drug: Raltegravir

Interventions

Raltegravir DRUG

One 400mg tablet on day 1.

Also known as: ISENTRESS, 400mg

Raltegravir

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Changi General Hospital: lead
• National University Hospital, Singapore: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Changi General Hospital

Singapore, Singapore, 529889, Singapore

Location

Related Publications (6)

• Barry MG, Khoo SH, Veal GJ, Hoggard PG, Gibbons SE, Wilkins EG, Williams O, Breckenridge AM, Back DJ. The effect of zidovudine dose on the formation of intracellular phosphorylated metabolites. AIDS. 1996 Oct;10(12):1361-7. doi: 10.1097/00002030-199610000-00008.

  PMID: 8902065 BACKGROUND

• Long MC, Bennetto-Hood C, Acosta EP. A sensitive HPLC-MS-MS method for the determination of raltegravir in human plasma. J Chromatogr B Analyt Technol Biomed Life Sci. 2008 May 15;867(2):165-71. doi: 10.1016/j.jchromb.2008.03.022. Epub 2008 Apr 1.

  PMID: 18430616 BACKGROUND

• Ter Heine R, Hillebrand MJ, Rosing H, van Gorp EC, Mulder JW, Beijnen JH, Huitema AD. Quantification of the HIV-integrase inhibitor raltegravir and detection of its main metabolite in human plasma, dried blood spots and peripheral blood mononuclear cell lysate by means of high-performance liquid chromatography tandem mass spectrometry. J Pharm Biomed Anal. 2009 Feb 20;49(2):451-8. doi: 10.1016/j.jpba.2008.11.025. Epub 2008 Nov 27.

  PMID: 19128911 BACKGROUND

• Wenning LA, Hanley WD, Brainard DM, Petry AS, Ghosh K, Jin B, Mangin E, Marbury TC, Berg JK, Chodakewitz JA, Stone JA, Gottesdiener KM, Wagner JA, Iwamoto M. Effect of rifampin, a potent inducer of drug-metabolizing enzymes, on the pharmacokinetics of raltegravir. Antimicrob Agents Chemother. 2009 Jul;53(7):2852-6. doi: 10.1128/AAC.01468-08. Epub 2009 May 11.

  PMID: 19433563 BACKGROUND

• 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

  BACKGROUND

• Merck &Co Inc. (2007). Isentress (raltegravir) tablets. FDA approved label.

  BACKGROUND

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

Raltegravir Potassium

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Edmund JD Lee, Professor

  Changi General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: December 4, 2009
• First Posted: December 7, 2009
• Study Start: December 1, 2009
• Primary Completion: March 1, 2010
• Study Completion: March 1, 2010
• Last Updated: March 19, 2010

Record last verified: 2010-03

Locations

SG (1)