Clinical trial NCT01551316: Safety Study to Evaluate MN-221 in Chronic Obstructive Pulmonary Disease (COPD) Patients
Official title: A Phase Ib Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety of Repeated Administration, Intravenous MN-221 in Stable Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Chronic Obstructive Pulmonary Disease
Keywords: safety
pharmacokinetics
spirometry
Lead sponsor: MediciNova
Sponsor class: INDUSTRY
First posted: 2012-03-12
Enrollment: 19
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: In MediciNova's clinical development plan for MN-221, it was recognized that treatment of COPD exacerbations may necessitate more than one single i.v. infusion and that patients in this population may have more co-morbidities (and concomitant medications) than has been generally studied so far. Thus, the primary objective of this clinical study is to determine the repeated administration safety and tolerability of intravenous (i.v.) MN-221 compared to placebo with repeated administration over several days in moderate to severe COPD patients who may also have co-morbidities and concomitant medications (CM) common in this population. Secondary outcomes include pharmacokinetics (PK) and preliminary efficacy (FEV1).

This Phase 1b trial follows naturally upon a Phase 1b COPD trial completed last year (MN-221-CL-010) and is additionally well-supported by relevant animal safety data and human clinical trial information.


Eligibility criteria: Inclusion Criteria:

* Male or female 40-75 years of age, inclusive;
* History of physician-diagnosed (e.g., by clinical history, \>15-pack year history of smoking, physical examination, and spirometry) COPD treated for ≥ 3 months prior to Visit 1 Pre-Screening;
* FEV1 ≥ 30% and \< 80% predicted and FEV1/FVC ratio \< 0.7 at Visit 1 Pre-Screening and Visit 2 Screening;
* Negative urine pregnancy test for all females unless the subject is post-menopausal (≥ 24 months of spontaneous amenorrhea) or surgically sterile (hysterectomy, bilateral ovariectomy or bilateral tubal ligation);
* Negative urine drug screen for cocaine, phencyclidine (PCP), methamphetamine;
* Negative alcohol breath test;
* Electrocardiogram (ECG) without serious abnormality and with QTcB and QTcF \< 460 milliseconds (msec);
* Ability to wash-out of concomitant LABA and Theophylline, if ongoing, for 7-8 days (i.e., Visit 2 Screening through 5-Day Treatment Period).
* Legally effective written informed consent obtained prior to starting any study procedures.
* Subject willing and able to comply with the protocol and procedures, as judged by Investigator.

Exclusion Criteria:

* Sustained release methylxanthine (e.g. Theophylline) or long acting beta agonists ≤ 48 hours prior to treatment start (Day 1);
* Acute exacerbation of COPD requiring emergency treatment ≤ 30 days of screening or hospitalization ≤ 60 days of Visit 2 Screening;
* Antibiotic therapy for respiratory infection ≤ 15 days of Visit 2 Screening;
* Presence of active respiratory disease such as pneumonia and acute exacerbation of chronic bronchitis;
* Hypokalemia defined as a potassium level \<3.0 mmol/L at Visit 2 Screening. note: Subjects \<3.0 mmol/L may be re-screened at Visit 2 Screening after receiving potassium replacement therapy;
* Significant clinical laboratory abnormality that, in the opinion of the Investigator, may put the subject at risk;
* Significant renal, hepatic, endocrine, neurologic or other systemic disease that, in the opinion of the Investigator, may put the subject at undue risk;
* Uncontrolled hypertension (defined as a blood pressure ≥ 170/100 mm Hg at Visit 1 Pre-Screening) and/or uncontrolled angina, uncontrolled diabetes, uncontrolled congestive heart failure (CHF), uncontrolled serious arrhythmia;
* Myocardial infarction within 6 months of treatment start;
* Pregnant or lactating females;
* Participation in another clinical study with an investigational drug within 30 days of Visit 1 Pre-Screening;
* Patients with home oxygen requirements.
* A known allergy to excipients of the MN-221 drug product;
* A known allergy to other beta agonists;
* Currently on medication/s that are recognized to have risk of Torsades de Pointes

Primary outcomes:
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
timeFrame: Treatment Days 1- 5
Secondary outcomes:
measure: MN-221 and primary metabolite levels will be analyzed by liquid chromatography/mass spectrometry/mass spectrometry.
timeFrame: Treatment Days 1-5
measure: Evaluation of respiratory parameters (FEV1, peak flow, accessory muscle use, respiratory rate)
timeFrame: Screening, Treatment Days 1,3,5
Other outcomes:
Locations:
city: New Braunfels
country: United States
facility: Central Texas Health Research
state: Texas
city: San Antonio
country: United States
facility: Sylvana Research Associates
state: Texas
Study officials:
References: