A Study to Determine if Technosphere® Inhalation Powder (FDKP) Causes ECG Changes (QTc) Following the Medication's Inhaled Administration.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Mannkind Corporation
ClinicalTrials.gov Identifier:
NCT00721344
First received: July 22, 2008
Last updated: June 12, 2012
Last verified: June 2012

July 22, 2008
June 12, 2012
April 2008
August 2008   (final data collection date for primary outcome measure)
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 ]
Same as current
Complete list of historical versions of study NCT00721344 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
A Study to Determine if Technosphere® Inhalation Powder (FDKP) Causes ECG Changes (QTc) Following the Medication's Inhaled Administration.
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

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.

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.

Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Healthy Subjects
  • 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
  • Experimental: 1
    Interventions:
    • Drug: Technosphere Inhalation Powder (FDKP)
    • Drug: Moxifloxacin
    • Drug: Technosphere Inhalation Powder (FDKP)
    • Drug: Placebo
  • Experimental: 2
    Interventions:
    • Drug: Technosphere Inhalation Powder (FDKP)
    • Drug: Moxifloxacin
    • Drug: Technosphere Inhalation Powder (FDKP)
    • Drug: Placebo
  • Experimental: 3
    Interventions:
    • Drug: Technosphere Inhalation Powder (FDKP)
    • Drug: Moxifloxacin
    • Drug: Technosphere Inhalation Powder (FDKP)
    • Drug: Placebo
  • Experimental: 4
    Interventions:
    • Drug: Technosphere Inhalation Powder (FDKP)
    • Drug: Moxifloxacin
    • Drug: Technosphere Inhalation Powder (FDKP)
    • Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
48
October 2008
August 2008   (final data collection date for primary outcome measure)

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
Both
18 Years to 45 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00721344
MKC-T-131
Not Provided
Mannkind Corporation
Mannkind Corporation
Not Provided
Not Provided
Mannkind Corporation
June 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP