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
  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 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 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

Resource links provided by NLM:


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 ]

Enrollment: 48
Study Start Date: April 2008
Study Completion Date: October 2008
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 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: 2 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: 3 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: 4 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
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: NCT00721344

Locations
United States, Washington
Charles River Clinical Services Northwest
Tacoma, Washington, United States, 98418
Sponsors and Collaborators
Mannkind Corporation
  More Information

No publications provided

Responsible Party: Mannkind Corporation
ClinicalTrials.gov Identifier: NCT00721344     History of Changes
Other Study ID Numbers: MKC-T-131
Study First Received: July 22, 2008
Last Updated: June 12, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Mannkind Corporation:
Healthy males and females

Additional relevant MeSH terms:
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 August 21, 2014