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

MannKind

Status and phase: Completed; Phase 1

Conditions: Healthy Subjects

Treatments: Drug: Placebo; Drug: Moxifloxacin; Drug: Technosphere Inhalation Powder (FDKP)

Study type: Interventional

Funder types: Industry

Identifiers

NCT00721344

MKC-T-131

Details and patient eligibility

About

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.

Full 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.

Enrollment: 48 patients

Sex: All

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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48 participants in 4 patient groups

1

Experimental group

Treatment:

Drug: Placebo

Drug: Technosphere Inhalation Powder (FDKP)

Drug: Moxifloxacin

Drug: Technosphere Inhalation Powder (FDKP)

2

Experimental group

Treatment:

Drug: Placebo

Drug: Technosphere Inhalation Powder (FDKP)

Drug: Moxifloxacin

Drug: Technosphere Inhalation Powder (FDKP)

3

Experimental group

Treatment:

Drug: Placebo

Drug: Technosphere Inhalation Powder (FDKP)

Drug: Moxifloxacin

Drug: Technosphere Inhalation Powder (FDKP)

4

Experimental group

Treatment:

Drug: Placebo

Drug: Technosphere Inhalation Powder (FDKP)

Drug: Moxifloxacin

Drug: Technosphere Inhalation Powder (FDKP)