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Trial record 48 of 116 for:    Atenolol

Clinical Study to Investigate Safety and Effects on Heart Rate, Blood Pressure, and Pharmacokinetic Interactions of ACT-334441

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ClinicalTrials.gov Identifier: NCT02479204
Recruitment Status : Terminated (Based on results from the pilot phase, the study is terminated. No safety events leading to discontinuation were reported)
First Posted : June 24, 2015
Last Update Posted : July 10, 2018
Sponsor:
Information provided by (Responsible Party):
Idorsia Pharmaceuticals Ltd.

Brief Summary:
The aim of the study is to investigate the safety of the concomitant administration of ACT-334441 with cardiovascular drugs.

Condition or disease Intervention/treatment Phase
Healthy Subjects Drug: ACT-334441 2 mg Drug: ACT-334441 4 mg Drug: Placebo Drug: Atenolol Drug: Diltiazem ER Phase 1

Detailed Description:
The study will consist of two parts: a pilot part (Part A) that will be completed prior to the start of the main part (Part B). The Subjects who will participate in Part A are excluded from Part B.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Single-center, Open-label, Randomized, Multiple-dose, Parallel-group Study to Investigate Safety and Effects on Heart Rate, Blood Pressure, and Pharmacokinetic Interactions of ACT-334441 Combined With Calcium-channel Blocker (Diltiazem) or Beta-blocker (Atenolol) Treatment in Healthy Subjects
Actual Study Start Date : April 28, 2015
Actual Primary Completion Date : May 1, 2016
Actual Study Completion Date : May 1, 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Part A ACT-334441 + atenolol
4 subjects will receive 50 mg of atenolol once daily for 6 days, and a concomitant single administration of ACT-334441 2 mg on Day 6
Drug: ACT-334441 2 mg
capsule containing ACT-334441 at a strength of 2 mg

Drug: Atenolol
film-coated tablet containing atenolol at a strength of 50 mg
Other Name: Tenormine

Experimental: Part A ACT-334441 + diltiazem
4 subjects will receive 240 mg of diltiazem once daily for 6 days, and a concomitant single administration of ACT-334441 2 mg on Day 6
Drug: ACT-334441 2 mg
capsule containing ACT-334441 at a strength of 2 mg

Drug: Diltiazem ER
film-coated tablet containing diltiazem at a strength of of 120 mg
Other Name: Bi-tildiem

Experimental: Part B ACT-334441 + atenolol
12 subjects will receive 50 mg of atenolol (once daily) from day 1 to day 15, placebo once on day 6, and ACT-334441 4 mg (once daily) from day 8 to day 15
Drug: ACT-334441 4 mg
capsule containing ACT-334441 at a strength of 4 mg

Drug: Placebo
ACT-33441-matching placebo

Drug: Atenolol
film-coated tablet containing atenolol at a strength of 50 mg
Other Name: Tenormine

Experimental: Part B ACT-334441 + diltiazem
12 subjects will receive 240 mg of diltiazem (once daily) from day 1 to day 15, placebo once on day 6, and ACT-334441 4 mg (once daily) from day 8 to day 15
Drug: ACT-334441 4 mg
capsule containing ACT-334441 at a strength of 4 mg

Drug: Placebo
ACT-33441-matching placebo

Drug: Diltiazem ER
film-coated tablet containing diltiazem at a strength of of 120 mg
Other Name: Bi-tildiem




Primary Outcome Measures :
  1. PR intervals measured by 12-lead ECG (Part A + Part B) [ Time Frame: Days 1 and 6 (Part A); Days 1, 6, 8, 9, 15, and 16 (Part B) ]
    Absolute PR intervals and corresponding changes from baseline at the different days of measurement

  2. Heart rate (HR) measured by 12-lead ECG (PArt A + Part B) [ Time Frame: Days 1 and 6 (Part A); Days 1, 6, 8, 9, 15, and 16 (Part B) ]
    Absolute heart rates at the different days of measurement

  3. Hourly mean heart rate (HR) measured by 24-hour Holter ECG [ Time Frame: Days 1 and 6 (Part A); Days 1, 6, 8, 9, 15, and 16 (Part B ]
    Absolute and change from baseline in hourly mean HR on each day of measurement


Secondary Outcome Measures :
  1. Areas under the plasma concentration-time curves (AUC) for ACT-334441, diltiazem and atenolol (Part B) [ Time Frame: Blood samples from Day 1 to Day 20 for the PK profile of diltiazem and atenolol, and from Day 8 to Day 21 for the PK profile of ACT-334441. ]
    AUCs will be calculated will be calculated according to the linear trapezoidal rule for the following periods: from zero to time t of the last measured concentration above the limit of quantification, from zero to 24h after study drug administration, from zero to infinity)

  2. Maximum plasma concentration (Cmax) for ACT-334441, diltiazem and atenolol (Part B) [ Time Frame: From Day 1 to Day 20 for diltiazem and atenolol; from Day 8 to Day 21 for ACT-33444. ]
    The measured individual concentrations of ACT-334441, diltiazem and atenolol will be used to obtain their respective Cmax

  3. Time to reach the maximum plasma concentration (tmax) for ACT-334441, diltiazem and atenolol (Part B) [ Time Frame: From Day 1 to Day 20 for diltiazem and atenolol; from Day 8 to Day 21 for ACT-33444 ]
    The measured individual concentrations of ACT-334441, diltiazem and atenolol will be used to obtain their respective tmax

  4. Terminal half-life [t(1/2)] of ACT-334441, diltiazem and atenolol (Part B) [ Time Frame: From Day 1 to Day 20 for diltiazem and atenolol; from Day 8 to Day 21 for ACT-33444 ]
    Time required for the plasma concentration of a drug to decrease by 50% in the final stage of its elimination

  5. Trough plasma levels (Ctrough) of of ACT-334441, diltiazem and atenolol (Part B) [ Time Frame: From Day 1 to Day 15 for diltiazem and atenolol; from Day 8 to Day 15 for ACT-33444 ]
    Ctrough will be used to determine the attainment of steady state conditions

  6. Number of subjects with adverse events as a measure of safety [ Time Frame: From baseline to end of study [Day 20-23 (Part A), Day 556-59 (Part B)] ]
    An AE is defined as any unfavorable and unintended sign, including an abnormal laboratory finding, symptom or disease, that occurs during the course of the study, whether or not considered related to the study drug


Other Outcome Measures:
  1. Lymphocyte count as a measure of immunomodulation (Part A + Part B) [ Time Frame: Day 1, Day 6, Day 12 and Day 20 (Part A); Day 1 and Day 8 toDay 16 (Part B) ]


Information from the National Library of Medicine

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Ages Eligible for Study:   25 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Signed informed consent
  • Body mass index (BMI) between 18.0 and 30.0 kg/m2 (inclusive) at screening.
  • Women of childbearing potential must have a negative pregnancy test and they must use reliable methods of contraception
  • Healthy on the basis of physical examination,cardiovascular assessments and laboratory tests

Exclusion Criteria:

  • Pregnant or lactating women
  • Any contraindication to the study drugs
  • History or presence of any disease or condition or treatment, which may put the subject at risk of participation in the study or may interfere with the absorption, distribution, metabolism or excretion of the study drugs
  • Any clinically significant abnormalities in laboratory tests, vital signs, ECG variables and pulmonary variables
  • Any circumstances or conditions, which, in the opinion of the investigator, may affect the subject's full participation in the study or compliance with the protocol

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02479204


Locations
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France
BIOTRIAL
Rennes, France, CS 34246
Sponsors and Collaborators
Idorsia Pharmaceuticals Ltd.

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Responsible Party: Idorsia Pharmaceuticals Ltd.
ClinicalTrials.gov Identifier: NCT02479204     History of Changes
Other Study ID Numbers: AC-064-102
First Posted: June 24, 2015    Key Record Dates
Last Update Posted: July 10, 2018
Last Verified: July 2018
Keywords provided by Idorsia Pharmaceuticals Ltd.:
safety
heart rate
pharmacokinetics
Additional relevant MeSH terms:
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Atenolol
Diltiazem
Anti-Arrhythmia Agents
Antihypertensive Agents
Sympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Adrenergic beta-1 Receptor Antagonists
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Calcium Channel Blockers
Membrane Transport Modulators
Calcium-Regulating Hormones and Agents
Vasodilator Agents