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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.

This study has been withdrawn prior to enrollment.
(strategic decision)
Sponsor:
Information provided by (Responsible Party):
Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier:
NCT00908414
First received: May 21, 2009
Last updated: October 27, 2016
Last verified: October 2016
  Purpose
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).

Condition Intervention Phase
HIV Infections
Drug: TMC589337 40 mg
Drug: TMC589337 100 mg
Drug: TMC589337 200 mg
Drug: TMC589337 400 mg
Drug: TMC589354 40 mg
Drug: TMC589354 100 mg
Drug: TMC589354 200 mg
Drug: TMC589354 400 mg
Drug: TMC589337 AA mg
Drug: TMC589354 BB mg
Drug: TMC589337 CC mg
Drug: TMC589354 DD mg
Drug: TMC589337 EE mg
Drug: TMC589354 YY mg
Drug: TMC310911 300 mg
Drug: TMC310911 600 mg
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Treatment
Official Title: Phase I, Double-blind, Randomized, Placebo-controlled Trial in Healthy Volunteers to Examine Safety, Tolerability, Plasma Pharmacokinetics of TMC589337&TMC589354 After Increasing Single Oral Doses & in an Open-label Part After Different Repeated Doses in Combination With Single Oral Dose of TMC310911

Resource links provided by NLM:


Further study details as provided by Tibotec Pharmaceuticals, Ireland:

Primary Outcome Measures:
  • 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. [ Time Frame: 8 weeks. This includes a treatment, washout and follow up period and is excluding screening period of maximum 21 days before first medication intake) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The trial objectives are to determine the safety, tolerability and plasma pk interaction between TMC310911 and TMC589337 or TMC589354. [ Time Frame: 8 weeks. This includes a treatment, washout and follow up period and is excluding screening period of maximum 21 days before first medication intake) ] [ Designated as safety issue: No ]

Enrollment: 0
Study Start Date: May 2009
Estimated Study Completion Date: October 2009
Estimated Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Panel 1: Single Dose Escalation
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
Participants will receive TMC589337 40 mg in Session Ia of Panel 1.
Drug: TMC589337 100 mg
Participants will receive TMC589337 100 mg in Session IIa of Panel 1.
Drug: TMC589337 200 mg
Participants will receive TMC589337 200 mg in Session IIIa of Panel 1.
Drug: TMC589337 400 mg
Participants will receive TMC589337 400 mg in Session IVa of Panel 1.
Drug: Placebo
Participants will receive matching placebo to TMC589337 or TMC589354 in Panel 1 and 2.
Experimental: Panel 2: Single Dose Escalation
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
Participants will receive TMC589354 40 mg in Session Ib of Panel 2.
Drug: TMC589354 100 mg
Participants will receive TMC589354 100 mg in Session IIb of Panel 2.
Drug: TMC589354 200 mg
Participants will receive TMC589354 200 mg in Session IIIb of Panel 2.
Drug: TMC589354 400 mg
Participants will receive TMC589354 400 mg in Session IVb of Panel 2.
Drug: Placebo
Participants will receive matching placebo to TMC589337 or TMC589354 in Panel 1 and 2.
Experimental: Panel 3: Multiple dosing
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
Participants will receive TMC589337 AA mg on Days 1 to 7 in Session Va of Panel 3.
Drug: TMC310911 300 mg
Participants will receive TMC310911 300 mg in Panel 3, 4, 5, 6 and 7.
Experimental: Panel 4: Multiple dosing
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
Participants will receive TMC589354 BB mg on Days 1 to 7 in Session Vb of Panel 4.
Drug: TMC310911 300 mg
Participants will receive TMC310911 300 mg in Panel 3, 4, 5, 6 and 7.
Experimental: Panel 5: Multiple dosing
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
Participants will receive TMC589337 CC mg on Days 1 to 7 in Session VIa of Panel 5.
Drug: TMC310911 300 mg
Participants will receive TMC310911 300 mg in Panel 3, 4, 5, 6 and 7.
Experimental: Panel 6: Multiple dosing
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
Participants will receive TMC589354 DD mg on Days 1 to 7 in Session VIb of Panel 6.
Drug: TMC310911 300 mg
Participants will receive TMC310911 300 mg in Panel 3, 4, 5, 6 and 7.
Experimental: Panel 7: Multiple dosing
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
Participants will receive TMC589337 EE mg on Days 1 to 7 in Session VII of Panel 7.
Drug: TMC589354 YY mg
Participants will receive TMC589354 YY mg on Days 1 to 7 in Session VII of Panel 7.
Drug: TMC310911 300 mg
Participants will receive TMC310911 300 mg in Panel 3, 4, 5, 6 and 7.
Drug: TMC310911 600 mg
Participants will receive TMC310911 600 mg in Panel 7.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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).

Exclusion Criteria:

  • 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.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00908414

Locations
Netherlands
Utrecht, Netherlands
Sponsors and Collaborators
Tibotec Pharmaceuticals, Ireland
Investigators
Study Director: Tibotec Pharmaceuticals Limited Clinical Trial Tibotec Pharmaceutical Limited
  More Information

Responsible Party: Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier: NCT00908414     History of Changes
Other Study ID Numbers: CR016195  PEPI-TIDP23-C104 
Study First Received: May 21, 2009
Last Updated: October 27, 2016
Health Authority: Ireland: Irish Agriculture and Food Development Authority

Keywords provided by Tibotec Pharmaceuticals, Ireland:
PEPI-TiDP23-C104
PEPI-C104
PEPI
TMC589337
TMC589354
TMC310911
Healthy Volunteers

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases

ClinicalTrials.gov processed this record on December 07, 2016