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

Healthy Subjects Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00721344
• Other study ID #: MKC-T-131
• Status: Completed
• Phase: Phase 1
• First received: July 22, 2008
• Last updated: June 12, 2012
• Start date: April 2008
• Est. completion date: October 2008

Study information

• Verified date: June 2012
• Source: Mannkind Corporation
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: October 2008
• Est. primary completion date: August 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 45 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Healthy Subjects

Intervention

Drug:
• Technosphere Inhalation Powder (FDKP)
Technosphere® Inhalation Powder 20mg
• Moxifloxacin
Tablets 400mg
• Technosphere Inhalation Powder (FDKP)
Technosphere® Inhalation Powder 40mg
• Placebo
Placebo cartridges

Locations

Country	Name	City	State
United States	Charles River Clinical Services Northwest	Tacoma	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Mannkind Corporation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary endpoint is the time-matched, placebo-subtracted change from baseline in QTc after a supratherapeutic dose of Technosphere Inhalation Powder		11 days	Yes
Secondary	The time-matched change from baseline in QTc after therapeutic dose Technosphere® Inhalation Powder based on an individual correction (QTcI) method.		11 days	Yes
Secondary	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.		11 Days	Yes
Secondary	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.		11 Days	Yes
Secondary	Change in ECG morphological patterns		11 Days	Yes
Secondary	Heart rate and RR interval.		11 Days	Yes
Secondary	PR interval.		11 Days	Yes
Secondary	QRS interval.		11 Days	Yes
Secondary	Correlation between the QTcI change from baseline and plasma concentrations of FDKP.		11 Days	Yes
Secondary	Plasma concentrations of FDKP.		11 Days	Yes