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

Primary Purpose

Healthy Subjects

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Technosphere Inhalation Powder (FDKP)
Moxifloxacin
Technosphere Inhalation Powder (FDKP)
Placebo
Sponsored by
Mannkind Corporation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Healthy Subjects focused on measuring Healthy males and females

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesAccepts 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

Sites / Locations

  • Charles River Clinical Services Northwest

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

1

2

3

4

Arm Description

Outcomes

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

Secondary Outcome Measures

The time-matched change from baseline in QTc after therapeutic dose Technosphere® Inhalation Powder based on an individual correction (QTcI) method.
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.
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.
Change in ECG morphological patterns
Heart rate and RR interval.
PR interval.
QRS interval.
Correlation between the QTcI change from baseline and plasma concentrations of FDKP.
Plasma concentrations of FDKP.

Full Information

First Posted
July 22, 2008
Last Updated
June 12, 2012
Sponsor
Mannkind Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT00721344
Brief Title
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

2. Study Status

Record Verification Date
June 2012
Overall Recruitment Status
Completed
Study Start Date
April 2008 (undefined)
Primary Completion Date
August 2008 (Actual)
Study Completion Date
October 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mannkind Corporation

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Healthy Subjects
Keywords
Healthy males and females

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
48 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Title
2
Arm Type
Experimental
Arm Title
3
Arm Type
Experimental
Arm Title
4
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Technosphere Inhalation Powder (FDKP)
Intervention Description
Technosphere® Inhalation Powder 20mg
Intervention Type
Drug
Intervention Name(s)
Moxifloxacin
Intervention Description
Tablets 400mg
Intervention Type
Drug
Intervention Name(s)
Technosphere Inhalation Powder (FDKP)
Intervention Description
Technosphere® Inhalation Powder 40mg
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo cartridges
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
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
Title
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
Title
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
Title
Change in ECG morphological patterns
Time Frame
11 Days
Title
Heart rate and RR interval.
Time Frame
11 Days
Title
PR interval.
Time Frame
11 Days
Title
QRS interval.
Time Frame
11 Days
Title
Correlation between the QTcI change from baseline and plasma concentrations of FDKP.
Time Frame
11 Days
Title
Plasma concentrations of FDKP.
Time Frame
11 Days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Facility Information:
Facility Name
Charles River Clinical Services Northwest
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98418
Country
United States

12. IPD Sharing Statement

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