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A Study to Determine if Technosphere® Inhalation Powder (FDKP) Causes ECG Changes (QTc) Following the Medication's Inhaled Administration.
This study is currently recruiting participants.
Verified by Mannkind Corporation, July 2008
Sponsored by: Mannkind Corporation
Information provided by: Mannkind Corporation
ClinicalTrials.gov Identifier: NCT00721344
  Purpose

48 healthy adult male & female subjects will be enrolled in this study to determine the effect of Technosphere® Inhalation Powder (FDKP) on the QT interval of the EKG. Eligible subjects will be randomized into a dosing regimen after admission.


Condition Intervention Phase
Healthy Subjects
Drug: Technosphere Inhalation Powder (FDKP)
Drug: Moxifloxacin
Drug: Placebo
Phase I

Drug Information available for: Moxifloxacin Moxifloxacin hydrochloride
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Active Control, Crossover Assignment, Safety Study
Official Title: A Phase 1, Randomized, Double-Blind, Cross-Over, Placebo- and Active-Controlled Cardiac Safety Study of Therapeutic and Supratherapeutic Doses of Fumaryl Diketopiperazine Administered as Technosphere® Inhalation Powder in Healthy Subjects

Further study details as provided by Mannkind Corporation:

Primary Outcome Measures:
  • The primary endpoint is the time-matched, placebo-subtracted change from baseline in QTc after a supratherapeutic dose of Technosphere Inhalation Powder [ Time Frame: 11 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • The time-matched change from baseline in QTc after therapeutic dose Technosphere® Inhalation Powder based on an individual correction (QTcI) method. [ Time Frame: 11 days ] [ Designated as safety issue: Yes ]
  • The maximum change in time-matched, placebo-subtracted QT interval corrected by Fridericia formula (QTcF) and Bazett formula (QTcB), respectively, for supratherapeutic dose of Technosphere® Inhalation Powder. [ Time Frame: 11 Days ] [ Designated as safety issue: Yes ]
  • The maximum change in time-matched, placebo-subtracted QT/QTc intervals by Fridericia formula (QTcF), and by Bazett formula (QTcB), respectively, for therapeutic dose of Technosphere® Inhalation Powder. [ Time Frame: 11 Days ] [ Designated as safety issue: Yes ]
  • Change in ECG morphological patterns [ Time Frame: 11 Days ] [ Designated as safety issue: Yes ]
  • Heart rate and RR interval. [ Time Frame: 11 Days ] [ Designated as safety issue: Yes ]
  • PR interval. [ Time Frame: 11 Days ] [ Designated as safety issue: Yes ]
  • QRS interval. [ Time Frame: 11 Days ] [ Designated as safety issue: Yes ]
  • Correlation between the QTcI change from baseline and plasma concentrations of FDKP. [ Time Frame: 11 Days ] [ Designated as safety issue: Yes ]
  • Plasma concentrations of FDKP. [ Time Frame: 11 Days ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 48
Study Start Date: April 2008
Estimated Study Completion Date: September 2008
Estimated Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Experimental Drug: Technosphere Inhalation Powder (FDKP)
Technosphere® Inhalation Powder 20mg
Drug: Moxifloxacin
Tablets 400mg
Drug: Technosphere Inhalation Powder (FDKP)
Technosphere® Inhalation Powder 40mg
Drug: Placebo
Placebo cartridges
2: Experimental Drug: Technosphere Inhalation Powder (FDKP)
Technosphere® Inhalation Powder 20mg
Drug: Moxifloxacin
Tablets 400mg
Drug: Technosphere Inhalation Powder (FDKP)
Technosphere® Inhalation Powder 40mg
Drug: Placebo
Placebo cartridges
3: Experimental Drug: Technosphere Inhalation Powder (FDKP)
Technosphere® Inhalation Powder 20mg
Drug: Moxifloxacin
Tablets 400mg
Drug: Technosphere Inhalation Powder (FDKP)
Technosphere® Inhalation Powder 40mg
Drug: Placebo
Placebo cartridges
4: Experimental Drug: Technosphere Inhalation Powder (FDKP)
Technosphere® Inhalation Powder 20mg
Drug: Moxifloxacin
Tablets 400mg
Drug: Technosphere Inhalation Powder (FDKP)
Technosphere® Inhalation Powder 40mg
Drug: Placebo
Placebo cartridges

Detailed Description:

This is a Phase 1, randomized, double-blind, cross-over, placebo- and active-controlled cardiac safety study in 48 healthy subjects (both male and female subjects) designed to assess the effect of FDKP on cardiac repolarization, if any, following introduction of Technosphere® Inhalation Powder via inhalation. Each trial subject will be administered 20 mg of FDKP, 40 mg of FDKP, 400 mg oral dose of moxifloxacin (active), and placebo in a crossover design during an 11 day in-patient stay.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Pulmonary Function Tests (PFTs) results within study specified limits.
  • Female subjects of childbearing potential must be non-pregnant and non-lactating and have a negative serum pregnancy test prior to enrollment into the trial.
  • Body Mass Index = 19 and = 30 kg/m2
  • Absence of recent drug or alcohol abuse
  • Able to provide written informed consent, follow study procedures and remain in-patient for the entire treatment period
  • Non-smoking (> 6 months)

Exclusion Criteria:

  • History of significant renal, pulmonary, rheumatological, hematological, neurological or psychiatrics disorder
  • Clinically significant major organ disease
  • Evidence or history of clinically significant allergies (except for untreated, asymptomatic, seasonal allergies at time of dosing);
  • Current or previous chemotherapy or radiation therapy that could cause lung toxicity
  • History of diabetes or taking any medications to treat diabetes
  • Clinically significant abnormal findings on physical exam, ECG, vital signs, clinical laboratory testing and medical history
  • Hypokalemia (calcium below lower limit of normal).
  • Previous exposure to Technosphere® Inhalation Powder
  • Participation in another clinical trial of an investigational drug or device within 30 days prior to Visit 3
  • Significantly excessive consumption of food or beverages with xanthine or caffeine
  • Unwilling to avoid alcohol 48 hours prior to study enrollment and during study
  • Unwilling to avoid strenuous activity for 48 hours prior to study enrollment and during study
  • Positive HIV or Hepatitis test
  • Any acute illness or fever within 72 hours of study dosing
  • Medication use (with exception of acetaminophen and hormonal birth control) or herbal use within 7 days of Visit 2
  • Unwillingness to remain in a quiet, controlled environment (i.e., no TV, music, games, etc during specific timepoints) or unwilling to remain supine during specific timepoints
  • Unwillingness to consume a study-specific diet
  • Blood donation within 8 weeks prior to Visit 2
  • History of chronic obstructive pulmonary disease (COPD), clinically proven asthma and/or any other clinically important pulmonary disease confirmed by pulmonary function testing and/or radiological finding
  • Active respiratory infection or persistent symptoms of such infection
  • History of risk factors for Torsades de pointes (TdP) [e.g., heart failure, hypokalemia, family history (parents or siblings) of Long QT Syndrome], history of fainting, unexplained loss of consciousness or convulsions
  • History of cardiac arrhythmia, of taking anti-arrhythmia drugs, significant cardiovascular dysfunction, myocardial dysfunction, cardiac surgery, transient attacks of ischemia or cerebrovascular accidents
  • An abnormal screening ECG which is interpreted by the Clinical Site Investigator to be clinically significant
  • Sustained supine resting systolic blood pressure > 140 mm Hg or < 100 mm Hg and /or diastolic blood pressure >95 mm Hg at study entry Baseline pulse rate of < 45 beats per minute or > 100 beats per minute
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00721344

Locations
United States, Washington
Charles River Clinical Services Northwest Recruiting
Tacoma, Washington, United States, 98418
Contact: Robin Downey     253-593-5304     robin.downey@crl.com    
Sponsors and Collaborators
Mannkind Corporation
  More Information

Responsible Party: Charles River Cinical Services - Northwest Kinetics ( Robin L. Downey, MD )
Study ID Numbers: MKC-T-131
Study First Received: July 22, 2008
Last Updated: July 22, 2008
ClinicalTrials.gov Identifier: NCT00721344  
Health Authority: United States: Food and Drug Administration

Keywords provided by Mannkind Corporation:
Healthy males and females

Study placed in the following topic categories:
Moxifloxacin
Healthy

Additional relevant MeSH terms:
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009