PEPI-TiDP23-C103: First-in-Human Study to Examine the Safety, Tolerability, and Plasma Pharmacokinetics of Increasing Single and Repeated Oral Doses of TMC558445 and of a Combined Single Day Dosing of Oral TMC558445 and Oral TMC310911 and Also Oral Darunavir

NCT00838760 | Completed Phase 1

• 1 other identifier: CR015955
• Study Type: interventional
• Target: 54
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of the study is to determine the safety, tolerability and plasma pharmacokinetics (pk) (i.e., the levels of TMC558445 circulating in your blood over time) of increasing single oral doses of TMC558445 and of multiple increasing oral doses followed by a single dose of TMC310911 to assess the potential boosting effect on the latter compound. In this study, two investigational new drugs are involved, TMC558445 and TMC310911. The study has been amended as follows: TMC558445 will be administered either twice a day (b.i.d.) or once daily (q.d.). A single 300 mg or 600 mg dose of TMC310911 will be administered under fasted or fed conditions. The boosting effect on Darunavir will be investigated.

Conditions

HIV-1

Keywords

PEPI-TiDP23-C103; PEPI-C103; PEPI; TMC558445; TMC310911; Darunavir, Healthy volunteers; Pharmacokinetics; HIV Infections

Outcome Measures

Primary Outcomes (1)

• The trial objectives are to determine the safety, tolerability and plasma pharmacokinetics of TMC558445 after increasing single oral doses from 40 mg up to 1600 mg or up to the MTD and after increasing multiple oral doses at 3 dose levels.

  safety & tolerability will be determined throughout the study. PK profiles of TMC558445 will be determined up to a max of 72 h after the last intake per session. Pk profiles of TMC310911/ DRV will be determined over 24 h.

Secondary Outcomes (3)

• To determine the potential food effect on a single oral dose of TMC558445 at one dose level

  4 days

• The safety and tolerability and the plasma pharmacokinetics of the repeated dosing for 7days of TMC558445 and a single 300 or 600mg dose of TMC310911 on Day7

  7 days

• The safety and tolerability and the plasma pharmacokinetics of the repeated dosing for 7days of TMC558445 and a single 800mg dose of DRV on Day7

  7 days

Interventions

TMC558445; TMC310911; Darunavir; Placebo DRUG

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Nonsmokers for at least 3 months prior to selection
• Weight as defined by a Body Mass Index (BMI, weight in kg divided by the square of height in meters) of 18.0 to 30.0 kg/m2, extremes included
• Informed Consent Form (ICF) signed voluntarily
• Able to comply with protocol requirements
• Healthy on the basis of a pretrial physical examination, medical history, the results of blood biochemistry and hematology tests, a urinalysis, vital signs, and a 12-lead electrocardiogram (ECG)

You may not qualify if:

• Past history of clinically significant heart arrhythmias (extrasystoli, tachycardia at rest)
• Having baseline prolongation of QTc interval \> 450 ms, history of risk factors for Torsade de Pointes syndrome (hypokalemia, family history of long QT Syndrome)
• Female, except if postmenopausal for more than 2 years, or post-hysterectomy or post-surgical sterilization (without reversal operation)
• Currently active clinically relevant or significant underlying gastrointestinal, cardiovascular, nervous system, psychiatric, metabolic, renal, hepatic, respiratory, inflammatory, or infectious disease
• History of clinically relevant skin disease or allergy including drug allergy as well

Sponsors & Collaborators

• Tibotec Pharmaceuticals, Ireland: lead

MeSH Terms

Conditions

HIV Infections

Interventions

TMC-310911; Darunavir

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Carbamates; Acids, Acyclic; Carboxylic Acids; Sulfones; Sulfur Compounds; Furans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Tibotec Pharmaceuticals Clinical Trial

  Tibotec Pharmaceutical Limited

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: February 5, 2009
• First Posted: February 6, 2009
• Study Start: February 1, 2009
• Primary Completion: October 1, 2009
• Study Completion: October 1, 2009
• Last Updated: April 28, 2010

Record last verified: 2010-04