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TMC435-TiDP16-C112 - Interaction Trial With Antidepressants

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier:
NCT01090700
First received: March 11, 2010
Last updated: April 8, 2013
Last verified: April 2013
  Purpose

The purpose of this study is to investigate the effect of steady-state concentrations of TMC435 150mg q.d. (once a day) on the steady-state pharmacokinetics of escitalopram 10 mg q.d., and vice versa. Steady state is a term which means that the drug has been given long enough so that the plasma concentrations will remain the same with each subsequent dose. TMC435 is being investigated for the treatment of chronic hepatitis C virus (HCV) infection. Pharmacokinetics (pk) means how the drug is absorbed into the bloodstream, distributed in the body and eliminated from the body.


Condition Intervention Phase
Hepatitis C Virus
Drug: TMC435
Drug: Escitalopram
Drug: TMC435 + Escitalopram
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I, Open-label, Randomized, 3-way Crossover Trial in Healthy Subjects to Investigate the Pharmacokinetic Interaction Between TMC435 and Escitalopram at Steady-state

Resource links provided by NLM:


Further study details as provided by Tibotec Pharmaceuticals, Ireland:

Primary Outcome Measures:
  • To investigate the effect of stable blood levels of TMC 435 given 150 mg q.d. on the stable blood levels of escitalopram given 10 mg q.d. in healthy participants and vica versa. [ Time Frame: pk profiles of TMC435 will be measured up to 24 hours on Day 7 in Treatment A and C. Pharmacokinetic profiles of escitalopram will be measured up to 24 hours postdose on Day 7 of Treatment B and C. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The short-term safety and tolerability of coadministration of TMC435 and escitalopram in healthy participants (safety and tolerability criteria are the activity of the heart, blood pressure, pulse, physical examination, parameters in urine and blood) [ Time Frame: This will be determined throughout the study; Day-1 through Day 8 in each session, 1 week and 4-5 weeks after last medication intake ] [ Designated as safety issue: No ]

Enrollment: 20
Study Start Date: May 2010
Study Completion Date: September 2010
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 001
TMC435 TMC435 150 mg daily for 7 days
Drug: TMC435
TMC435 150 mg daily for 7 days
002
Escitalopram Escitalopram 10 mg daily for 7 days
Drug: Escitalopram
Escitalopram 10 mg daily for 7 days
Experimental: 003
TMC435 + Escitalopram TMC435 150 mg + escitalopram 10 mg daily for 7 days
Drug: TMC435 + Escitalopram
TMC435 150 mg + escitalopram 10 mg daily for 7 days

Detailed Description:

TMC435 is being investigated for treatment of chronic HCV infection, in combination with Peg-IFN (pegylated interferon) and RBV (ribavirin). Peg-IFN plus RBV are currently an accepted methods for treating HCV. Treatment with Peg-IFN plus RBV for HCV infection is associated with a high rate of depression. The results of this study will provide dosing recommendations for coadministration of TMC435 and escitalopram in HCV-infected patients. This is a Phase I, open-label (both participant and investigator know the name of the medication) , randomized (study medication assigned by chance), crossover trial in 18 healthy participants to investigate the pharmacokinetic interaction between escitalopram and TMC435, both at steady state. Steady state is a term which means that the drug has been given long enough so that the plasma concentrations will remain the same with each subsequent dose. The participants will receive three treatments (treatment A-B-C) in a randomized order. In Treatment A, participants will receive TMC435 150 mg q.d. In Treatment B, participants will receive escitalopram 10 mg q.d. In treatment C, participants will receive escitalopram 10 mg q.d. and TMC435 150 mg q.d. All treatments will be administered for 7 days and with food. There will be a washout period (a period where no treatment will be taken in view of having all the medication eliminated from the body before starting a new treatment) of at least 10 days between last intake of study medication in one session and first intake of study medication in the subsequent session. Pharmacokinetic profiles of the two compounds will be measured through blood samples taken at regular intervals during the study and safety and tolerability will be assessed during the study period and in follow-up. Safety and tolerability evaluations will be recorded at regular intervals throughout the trial period. Blood and urine samples, electrocardiogram (ECG) and vital signs (blood pressure and heart rate) will be taken at screening, before medication intake on days 1 and 7 and on Day 8 in each session and at the 2 follow up visits at 1 week and 4-5 weeks after last dose of drug in the last session. A physical examination will be performed at screening, on day -1 (= day before day of first medication intake in each session) and during the 2 follow up visits. On the morning before first medication intake (in the first session only) a blood sample will be taken to examine your CYP2C19 genes, which are responsible for the production of enzymes that determine the breakdown of drugs in your body. The results of this study will provide dosing recommendations for coadministration of TMC435 and escitalopram in HCV-infected patients. Participants will receive in treatment A TMC435 150 mg q.d., in treatment B participants will receive escitalopram 10 mg and in treatment C participants will receive escitalopram 10 mg q.d. + TMC435 150 mg q.d. All treatments will be administered for 7 days and with food.

  Eligibility

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

Inclusion Criteria:

  • Non-smokers for at least 3 months prior to screening
  • Healthy on the basis of physical examination, medical history, vital signs and 12-lead ECG performed at screening
  • Healthy on the basis of clinical laboratory tests performed at screening
  • Subjects must have signed an informed consent document indicating they understand the purpose of and procedures required for the study and are willing to participate in the study
  • Participants must have signed the ICF for pharmacogenetic research indicating willingness to participate in the pharmacogenetic component of the study.

Exclusion Criteria:

  • A positive human immunodeficiency virus - type 1 (HIV-1) or HIV-2 test at study screening
  • Hepatitis A, B, or C infection (confirmed by hepatitis A antibody immunoglobulin [IgM], hepatitis B surface antigen, or hepatitis C virus antibody, respectively) at screening
  • History of liver or renal (estimated creatinine clearance below 60 mL/min) insufficiency, significant cardiac, vascular, pulmonary, gastrointestinal (such as significant diarrhea, gastric stasis, or constipation that in the investigator's opinion could influence drug absorption or bioavailability), endocrine, neurologic, hematologic, rheumatologic, psychiatric and neoplastic or metabolic disturbances
  • Known allergies, hypersensitivity, or intolerance to TMC435 or its excipients
  • Received an investigational drug (including investigational vaccines) or used an investigational medical device within 60 days before the planned start of treatment
  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: NCT01090700

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

No publications provided

Responsible Party: Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier: NCT01090700     History of Changes
Other Study ID Numbers: CR017044
Study First Received: March 11, 2010
Last Updated: April 8, 2013
Health Authority: Ireland: Irish Agriculture and Food Development Authority

Keywords provided by Tibotec Pharmaceuticals, Ireland:
TMC435-TiDP16-C112
TMC435-C112
TMC435
HCV
Hepatitis C

Additional relevant MeSH terms:
Hepatitis
Hepatitis C
Digestive System Diseases
Flaviviridae Infections
Hepatitis, Viral, Human
Liver Diseases
RNA Virus Infections
Virus Diseases
Citalopram
Dexetimide
Anti-Dyskinesia Agents
Antidepressive Agents
Antidepressive Agents, Second-Generation
Antiparkinson Agents
Autonomic Agents
Central Nervous System Agents
Cholinergic Agents
Cholinergic Antagonists
Molecular Mechanisms of Pharmacological Action
Muscarinic Antagonists
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Parasympatholytics
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Agents
Serotonin Uptake Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014