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

NCT00777595 | Completed Phase 1

• 1 other identifier: CCD-0808-PR-0036
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

QTc; CHF 4226 HFA; pMDI; Carmoterol

Outcome Measures

Primary Outcomes (1)

• QTci

  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

Secondary Outcomes (3)

• QTcX interval (subject-specific correction of QTcF, QTcB and QTcH)

  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

• Plasma concentration (AUC, Cmax, Tmax)

  Each treatment period on dosing day at -0.75, 0.08, 0.25, 0.5, 1, 2, 4, 6, 8 and 12 hrs

• Urinary excretion (Ae)

  Each treatment period on day of dosing at -0.75, 0.58 and 24 hours.

Study Arms (4)

Treatment A

EXPERIMENTAL

Single therapeutic dose of CHF 4226 pMDI

Drug: CHF 4226 pMDI

Treatment B

EXPERIMENTAL

Single supratherapeutic dose of CHF 4226 pMDI

Drug: CHF 4226 pMDI

Treatment C

PLACEBO COMPARATOR

Single dose of placebo

Drug: Placebo

Treatment D

ACTIVE COMPARATOR

Single dose of moxifloxacin

Drug: Moxifloxacin

Interventions

CHF 4226 pMDI DRUG

Inhaled solution, single therapeutic dose

Also known as: Carmoterol HFA

Treatment A

Placebo DRUG

Inhaled solution, single dose of placebo

Treatment C

Moxifloxacin DRUG

Tablet, oral, 400mg, single dose

Also known as: Avelox

Treatment D

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Chiesi Farmaceutici S.p.A.: lead

Study Sites (1)

PRACS Institute, Ltd.

Fargo, North Dakota, 58104, United States

Location

Related Publications (3)

• Russell T, Riley SP, Cook JA, Lalonde RL. A perspective on the use of concentration-QT modeling in drug development. J Clin Pharmacol. 2008 Jan;48(1):9-12. doi: 10.1177/0091270007311115. No abstract available.

  PMID: 18094215 BACKGROUND

• Garnett CE, Beasley N, Bhattaram VA, Jadhav PR, Madabushi R, Stockbridge N, Tornoe CW, Wang Y, Zhu H, Gobburu JV. Concentration-QT relationships play a key role in the evaluation of proarrhythmic risk during regulatory review. J Clin Pharmacol. 2008 Jan;48(1):13-8. doi: 10.1177/0091270007307881.

  PMID: 18094216 BACKGROUND

• Bloomfield D, Krishna R. Commentary on the clinical relevance of concentration/QTc relationships for new drug candidates. J Clin Pharmacol. 2008 Jan;48(1):6-8. doi: 10.1177/0091270007312257. No abstract available.

  PMID: 18094214 BACKGROUND

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Moxifloxacin

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Robert I. Cooper, MD

  PRACS Institute, Ltd.

  PRINCIPAL INVESTIGATOR

• Steven E. Linberg, PhD

  Chiesi Farmaceutici S.p.A.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: October 20, 2008
• First Posted: October 22, 2008
• Study Start: October 1, 2008
• Primary Completion: December 1, 2008
• Study Completion: December 1, 2008
• Last Updated: March 27, 2009

Record last verified: 2009-03

Locations

US (1)