Evaluation of Possible Effects on the QTc Interval of CHF 4226 pMDI in Healthy Volunteers (CT14)

This study has been completed.
Sponsor:
Collaborator:
Chiesi Pharmaceuticals Inc.
Information provided by:
Chiesi Farmaceutici S.p.A.
ClinicalTrials.gov Identifier:
NCT00777595
First received: October 20, 2008
Last updated: March 26, 2009
Last verified: March 2009
  Purpose

The purpose of this study is to evaluate the effect of single doses of therapeutic and supratherapeutic doses of inhaled CHF 4226 pMDI on ventricular repolarization in healthy subjects compared with placebo.


Condition Intervention Phase
Chronic Obstructive Pulmonary Disease
Drug: CHF 4226 pMDI
Drug: Placebo
Drug: Moxifloxacin
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double Blind, Single Dose, Positive and Placebo Controlled, Crossover Study of the Effects of Inhaled Carmoterol, at the Proposed Therapeutic and Supratherapeutic Doses, on the QTc Intervals in Healthy Subjects

Resource links provided by NLM:


Further study details as provided by Chiesi Farmaceutici S.p.A.:

Primary Outcome Measures:
  • QTci [ Time Frame: ECGs taken every treatment period on day -1 and day +1 at -1, -0.5, -0.25, 0.08, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hrs ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • QTcX interval (subject-specific correction of QTcF, QTcB and QTcH) [ Time Frame: ECGs taken every treatment period on day -1 and day +1 at -1, -0.5, -0.25, 0.08, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hrs ] [ Designated as safety issue: Yes ]
  • Plasma concentration (AUC, Cmax, Tmax) [ Time Frame: Each treatment period on dosing day at -0.75, 0.08, 0.25, 0.5, 1, 2, 4, 6, 8 and 12 hrs ] [ Designated as safety issue: No ]
  • Urinary excretion (Ae) [ Time Frame: Each treatment period on day of dosing at -0.75, 0.58 and 24 hours. ] [ Designated as safety issue: No ]

Enrollment: 47
Study Start Date: October 2008
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment A
Single therapeutic dose of CHF 4226 pMDI
Drug: CHF 4226 pMDI
Inhaled solution, single therapeutic dose
Other Name: Carmoterol HFA
Experimental: Treatment B
Single supratherapeutic dose of CHF 4226 pMDI
Drug: CHF 4226 pMDI
Inhaled solution, single supratherapeutic dose
Other Name: Carmoterol HFA
Placebo Comparator: Treatment C
Single dose of placebo
Drug: Placebo
Inhaled solution, single dose of placebo
Other Name: Placebo
Active Comparator: Treatment D
Single dose of moxifloxacin
Drug: Moxifloxacin
Tablet, oral, 400mg, single dose
Other Name: Avelox

Detailed Description:

The secondary purposes of this study are to 1) determine if there is a relationship between the duration of the QTc intervals and the plasma concentrations of carmoterol; 2) expand the available information on plasma pharmacokinetics and urine excretion for inhaled carmoterol at the proposed therapeutic and supra-therapeutic doses; and 3) generate additional safety information.

  Eligibility

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

Inclusion Criteria:

  • Healthy adult male or female subjects, 18-55 years of age who provided written informed consent.
  • A body mass index (BMI) between 18 - 30, inclusive.
  • A normal blood pressure (< 140mmHg systolic and < 90mmHg diastolic)
  • A normal 12-lead ECG (QTcF interval < 450msec for males and < 470msec for females).
  • A serum potassium </= 4.0mEq/L.
  • A calculated creatinine clearance > 80mL/min.
  • Male subjects must agree to use a medically acceptable contraceptive (abstain from sexual intercourse, or use a condom with spermicide), have had a vasectomy at least 6 months prior to study participation or have a partner who is not of childbearing potential.

Exclusion Criteria:

  • A history or presence of significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or psychiatric disease.
  • A history of sensitivity or allergy to the quinolone class of antibiotics and/or a beta 2 adrenergic receptor agonist.
  • Clinically significant screening results (laboratory profiles, medical histories, ECGs, physical exam).
  • Hemoglobin below the normal reference range for the testing laboratory.
  • Abuse of alcohol or other substances.
  • Current use of tobacco products.
  • Subjects with a positive laboratory test result for hepatitis B, hepatitis C, HIV, controlled substances, cotinine or alcohol.
  • Any prescription medication taken within 14 days (or 5 elimination half-lives, whichever is longer) of Study Day -2, or have taken any over-the-counter medications, including topical medications, vitamins, herbal or dietary supplements/remedies (e.g., Saint John's Wort or Milk Thistle), within 14 days of Study Day -2, or planned concomitant medication while in the study (except for acetaminophen up to 2g/day), with the exception of hormonal birth control medications or hormone replacement therapy for females.
  • A history of additional risk factors for Torsade de Pointes (e.g., hypokalemia, history of drowning survival, family history of Long QT Syndrome, family history of Short QT Syndrome, or family history of unexplainable early sudden death).
  • Subject is pregnant or lactating female, or female at risk of pregnancy (i.e., not using an adequate contraceptive method: surgical sterilization [e.g., bilateral tubal ligation], hormonal contraception [implantable, patch, oral], IUD, and double-barrier methods [any double combination of: male or female condom with spermicidal gel, diaphragm, sponge, cervical dap]_.
  • Participation in a study of an investigational drug within 30 days prior to the baseline ECG.
  • Any condition that, in the judgment of the Investigator, would place a subject at undue risk, or potentially compromise the results or interpretation of the study.
  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: NCT00777595

Locations
United States, North Dakota
PRACS Institute, Ltd.
Fargo, North Dakota, United States, 58104
Sponsors and Collaborators
Chiesi Farmaceutici S.p.A.
Chiesi Pharmaceuticals Inc.
Investigators
Principal Investigator: Robert I. Cooper, MD PRACS Institute, Ltd.
Study Director: Steven E. Linberg, PhD Chiesi Pharmaceuticals Inc.
  More Information

Publications:
Responsible Party: Steven E. Linberg, Ph.D., Chiesi Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT00777595     History of Changes
Other Study ID Numbers: CCD-0808-PR-0036
Study First Received: October 20, 2008
Last Updated: March 26, 2009
Health Authority: United States: Food and Drug Administration

Keywords provided by Chiesi Farmaceutici S.p.A.:
QTc
CHF 4226 HFA
pMDI
Carmoterol

Additional relevant MeSH terms:
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases
Moxifloxacin
Norgestimate, ethinyl estradiol drug combination
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Contraceptives, Oral, Combined
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 18, 2014