PEPI-TiDP23-C104 is a First in Human Study With a Single Dose Escalation Part and a Multiple Dosing Part for Compounds TMC589337 and TMC589354.

NCT00908414 | Withdrawn Phase 1

• 2 other identifiers: CR016195PEPI-TIDP23-C104
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to determine the safety, tolerability, and plasma pharmacokinetics (i.e., the levels of TMC589337 and TMC589354 circulating in your blood over time) of increasing single oral doses of TMC589337 and TMC589354 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 3 investigational new drugs are involved. These new investigational drugs called TMC589337 and TMC589354 (from the PEPI family) and TMC310911 are in process of development for the treatment of Human Immunodeficiency Virus-Type 1 (HIV-1). TMC589337 and TMC589354 are novel molecules with no antiviral activity to be used to enhance the pharmacokinetics profile of a drug. TMC310911 is a novel and potent compound and belongs to a medication class called protease inhibitors (PI).

Conditions

HIV Infections

Keywords

PEPI-TiDP23-C104; PEPI-C104; PEPI; TMC589337; TMC589354; TMC310911; Healthy Volunteers

Outcome Measures

Primary Outcomes (1)

• The trial objectives are to determine the safety, tolerability and plasma pk of TMC589337/TMC589354 after increasing single oral doses from 40 mg up to 400 mg and after increasing multiple oral doses.

  8 weeks. This includes a treatment, washout and follow up period and is excluding screening period of maximum 21 days before first medication intake)

Secondary Outcomes (1)

• The trial objectives are to determine the safety, tolerability and plasma pk interaction between TMC310911 and TMC589337 or TMC589354.

  8 weeks. This includes a treatment, washout and follow up period and is excluding screening period of maximum 21 days before first medication intake)

Study Arms (7)

Panel 1: Single Dose Escalation

EXPERIMENTAL

Panel 1 will receive doses of 40 milligram (mg) (Session Ia), 100 mg (Session IIa), 200 mg (Session IIIa) and 400 mg (Session IVa) of TMC589337 or placebo.

Drug: TMC589337 40 mg; Drug: TMC589337 100 mg; Drug: TMC589337 200 mg; Drug: TMC589337 400 mg; Drug: Placebo

Panel 2: Single Dose Escalation

EXPERIMENTAL

Panel 2 will receive doses of 40 mg (Session Ib), 100 mg (Session IIb), 200 mg (Session IIIb) and 400 mg (Session IVb) of TMC589354 or placebo.

Drug: TMC589354 40 mg; Drug: TMC589354 100 mg; Drug: TMC589354 200 mg; Drug: TMC589354 400 mg; Drug: Placebo

Panel 3: Multiple dosing

EXPERIMENTAL

AA mg (Final doses will be selected based upon data obtained in the single dose sessions (i.e., Sessions I, II, and III) TMC589337 (n=6) b.i.d. (twice daily) during 7 days (Session Va) plus a single oral dose of 300 mg of TMC310911 on Day 7. After at least 14 days following Day 7 of multiple dosing, participants will receive 300 mg TMC310911, single dose (Session VIIIa).

Drug: TMC589337 AA mg; Drug: TMC310911 300 mg

Panel 4: Multiple dosing

EXPERIMENTAL

BB mg (final doses will be selected based upon data obtained in the single dose sessions (i.e., Sessions I, II, and III) TMC589354 (n=6) b.i.d. during 7 days (Session Vb) ) plus a single oral dose of 300 mg of TMC310911 on Day 7. After at least 14 days following Day 7 of multiple dosing, participants will receive 300 mg TMC310911, single dose (Session VIIIb).

Drug: TMC589354 BB mg; Drug: TMC310911 300 mg

Panel 5: Multiple dosing

EXPERIMENTAL

CC mg (final doses will be selected based upon data obtained in the single dose sessions (i.e., Sessions I, II, and III) TMC589337 (n=6) b.i.d. during 7 days (Session VIa) plus a single oral dose of 300 mg of TMC310911 on Day 7. After at least 14 days following Day 7 of multiple dosing, participants will receive 300 mg TMC310911, single dose (Session IXa).

Drug: TMC589337 CC mg; Drug: TMC310911 300 mg

Panel 6: Multiple dosing

EXPERIMENTAL

DD mg (final doses will be selected based upon data obtained in the single dose sessions (i.e., Sessions I, II, and III) TMC589354 (n=6) b.i.d. during 7 days (Session VIb) ) plus a single oral dose of 300 mg of TMC310911 on Day 7. After at least 14 days following Day 7 of multiple dosing, participants will receive 300 mg TMC310911, single dose (Session IXb).

Drug: TMC589354 DD mg; Drug: TMC310911 300 mg

Panel 7: Multiple dosing

EXPERIMENTAL

EE mg (final doses will be selected based upon data obtained in the single dose sessions (i.e., Sessions I, II, and III) TMC589337 (n=6) or YY mg TMC589354 (n=6) b.i.d. or q.d. during 7 days (Session VII) ) plus a single oral dose of 300 mg or 600mg of TMC310911 on Day 7. After at least 14 days following Day 7 of multiple dosing, participants will receive 300 mg or 600 mg TMC310911, single dose (Session X).

Drug: TMC589337 EE mg; Drug: TMC589354 YY mg; Drug: TMC310911 300 mg; Drug: TMC310911 600 mg

Interventions

TMC589337 40 mg DRUG

Participants will receive TMC589337 40 mg in Session Ia of Panel 1.

Panel 1: Single Dose Escalation

TMC589337 100 mg DRUG

Participants will receive TMC589337 100 mg in Session IIa of Panel 1.

Panel 1: Single Dose Escalation

TMC589337 200 mg DRUG

Participants will receive TMC589337 200 mg in Session IIIa of Panel 1.

Panel 1: Single Dose Escalation

TMC589337 400 mg DRUG

Participants will receive TMC589337 400 mg in Session IVa of Panel 1.

Panel 1: Single Dose Escalation

TMC589354 40 mg DRUG

Participants will receive TMC589354 40 mg in Session Ib of Panel 2.

Panel 2: Single Dose Escalation

TMC589354 100 mg DRUG

Participants will receive TMC589354 100 mg in Session IIb of Panel 2.

Panel 2: Single Dose Escalation

TMC589354 200 mg DRUG

Participants will receive TMC589354 200 mg in Session IIIb of Panel 2.

Panel 2: Single Dose Escalation

TMC589354 400 mg DRUG

Participants will receive TMC589354 400 mg in Session IVb of Panel 2.

Panel 2: Single Dose Escalation

TMC589337 AA mg DRUG

Participants will receive TMC589337 AA mg on Days 1 to 7 in Session Va of Panel 3.

Panel 3: Multiple dosing

TMC589354 BB mg DRUG

Participants will receive TMC589354 BB mg on Days 1 to 7 in Session Vb of Panel 4.

Panel 4: Multiple dosing

TMC589337 CC mg DRUG

Participants will receive TMC589337 CC mg on Days 1 to 7 in Session VIa of Panel 5.

Panel 5: Multiple dosing

TMC589354 DD mg DRUG

Participants will receive TMC589354 DD mg on Days 1 to 7 in Session VIb of Panel 6.

Panel 6: Multiple dosing

TMC589337 EE mg DRUG

Participants will receive TMC589337 EE mg on Days 1 to 7 in Session VII of Panel 7.

Panel 7: Multiple dosing

TMC589354 YY mg DRUG

Participants will receive TMC589354 YY mg on Days 1 to 7 in Session VII of Panel 7.

Panel 7: Multiple dosing

TMC310911 300 mg DRUG

Participants will receive TMC310911 300 mg in Panel 3, 4, 5, 6 and 7.

Panel 3: Multiple dosing; Panel 4: Multiple dosing; Panel 5: Multiple dosing; Panel 6: Multiple dosing; Panel 7: Multiple dosing

TMC310911 600 mg DRUG

Participants will receive TMC310911 600 mg in Panel 7.

Panel 7: Multiple dosing

Placebo DRUG

Participants will receive matching placebo to TMC589337 or TMC589354 in Panel 1 and 2.

Panel 1: Single Dose Escalation; Panel 2: Single Dose Escalation

Eligibility Criteria

• Age: 18 Years - 55 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 (extrasystolic, 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 posthysterectomy or postsurgical 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

Study Sites (1)

Unknown Facility

Utrecht, Netherlands

Location

MeSH Terms

Conditions

HIV Infections

Interventions

TMC-310911

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

Study Officials

• Tibotec Pharmaceuticals Limited Clinical Trial

  Tibotec Pharmaceutical Limited

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 21, 2009
• First Posted: May 25, 2009
• Study Start: May 1, 2009
• Primary Completion: October 1, 2009
• Study Completion: October 1, 2009
• Last Updated: October 28, 2016

Record last verified: 2016-10

Locations

NL (1)