Clinical trial NCT00721344: A Study to Determine if Technosphere® Inhalation Powder (FDKP) Causes ECG Changes (QTc) Following the Medication's Inhaled Administration.
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Keywords: Healthy males and females
Lead sponsor: Mannkind Corporation
Sponsor class: INDUSTRY
First posted: 2008-07-24
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: The primary endpoint is the time-matched, placebo-subtracted change from baseline in QTc after a supratherapeutic dose of Technosphere Inhalation Powder
timeFrame: 11 days
Secondary outcomes:
measure: The time-matched change from baseline in QTc after therapeutic dose Technosphere® Inhalation Powder based on an individual correction (QTcI) method.
timeFrame: 11 days
measure: 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.
timeFrame: 11 Days
measure: 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.
timeFrame: 11 Days
measure: Change in ECG morphological patterns
timeFrame: 11 Days
measure: Heart rate and RR interval.
timeFrame: 11 Days
measure: PR interval.
timeFrame: 11 Days
measure: QRS interval.
timeFrame: 11 Days
measure: Correlation between the QTcI change from baseline and plasma concentrations of FDKP.
timeFrame: 11 Days
measure: Plasma concentrations of FDKP.
timeFrame: 11 Days
Other outcomes:
Locations:
city: Tacoma
country: United States
facility: Charles River Clinical Services Northwest
state: Washington
Study officials:
References: