- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01550458
Safety Study of Mibefradil When Given Four Times a Day in Healthy Volunteers
A Study of the Pharmacokinetic and Safety Profile of QID Dosing of Mibefradil in Normal Human Volunteers
Study Overview
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Nebraska
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Lincoln, Nebraska, United States, 68502
- Celerion, Inc.
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Normal healthy volunteers aged 19 to 55 years, male or female, and willing and able to sign informed consent;
Females must have a negative pregnancy test at screening and be practicing a suitable method of birth control so that, in the opinion of the Investigator, they will not become pregnant during the course of the study, or females can be postmenopausal (no menstrual period for one year) or surgically sterilized. Females must either be sexually inactive (abstinent) for 14 days prior to Screening and remain so through 30 days following the final dosing of the study drug or have been using one of the following acceptable methods of birth control for the times specified:
- Barrier method (condom or diaphragm) with spermicidal for at least 14 days prior to Screening through Day -1 through 30 days following the final dosing of the study drug;
- Surgical sterilization (vasectomy) of partner at least 6 months prior to Day -1; or
- Females of non-childbearing potential have undergone one of the following sterilization procedures at least 6 months prior to Day -1: bilateral tubal ligation, hysterectomy, hysterectomy with unilateral or bilateral oophorectomy, or bilateral oophorectomy.
- Male subjects must continue to use their approved contraceptive method for 60 days after participating in the study.
- Has a body mass index (BMI) between 18.0 and 32.0 kg/m², inclusive; and
- Have no acute illnesses or chronic health issues that require medication.
Exclusion Criteria:
- History of investigational drug use within 30 days of this study;
- Subject has a clinically significant disorder that, in the opinion of the Investigator, could result in the subject's inability to understand and comply with the requirements of the study;
- History of hypertension, treated or untreated, or screening BP >140 mm Hg systolic or >90 mm Hg diastolic;
- Currently or within the last 14 days taking any medications (prescription, nonprescription, or herbal or Chinese remedies) including oral contraceptives and hormone replacement therapy;
- Subject has a history of impaired hepatic function that, in the Investigator's opinion, contraindicates participation in this study; or the subject has any other abnormal laboratory value of clinical significance for this study in the Investigators opinion;
- Current smoker (more than 10 cigarettes/day) for 6 months;
Subject has a creatinine clearance (CLcr) of less than 70 mL/min as calculated by the
Cockroft-Gault equation:
CLcr = ((140 - age) x body mass x [0.85 if female]) / (72 x creatinine)
where age is given in years, body mass is given in kg, and creatinine is given in mg/dL;
- Subject has a history, signs, or symptoms of ischemic cardiac, cerebrovascular, or peripheral vascular syndromes or other significant underlying cardiovascular disease that are clinically significant in the Investigator's opinion. This includes any known cardiac rhythm disorder or ECG abnormality;
- Subject, in the Investigator's opinion, is likely to have unrecognized cardiovascular disease, based on history or the presence of risk factors;
- Subject is currently taking or had taken in the previous 14 days, herbal preparations containing St. John's Wort (Hypericum perforatum);
- Subject has a history of allergic reactions to calcium channel antagonists;
- Females who are pregnant, actively trying to become pregnant, or lactating. Females must be practicing a suitable method of birth control (adequate barrier method of birth control; abstinence) so that, in the opinion of the Investigator, they will not become pregnant during the course of the study, or females can be postmenopausal (no menstrual period for one year) or surgically sterilized;
- Subject had a recent history (in the past 3 months) suggestive of evidence of alcohol or drug abuse or dependence, or has any unaccounted-for drug or alcohol in the original drug screen (tested positive);
- Allergy to latex or rubber;
- Hemoglobin under laboratory lower limit of normal; or
- Significant blood loss of 500 mL or greater or blood donation within 56 days prior to Day 1. Subjects cannot donate plasma within 5 days prior to Day 1.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Placebo
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1 out of 6 patients per cohort will receive placebo tablets identical in appearance and number to the active mibefradil arm.
Other Names:
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Experimental: Mibefradil
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25 mg tablets for oral administration given for 7 days at a total daily dose beginning at 100 mg per day divided into four doses.
Doses will be incremented in successive cohorts by 25 mg/day up to 400 mg/day.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Determine the safety of a 7-day course of oral mibefradil in four divided daily doses in normal healthy volunteers.
Time Frame: 7 days
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Safety will be assessed by clinical laboratory tests, physical examinations, vital sign measurements, continuous, real time, 3-lead ECG monitoring, concomitant medication documentation and adverse event monitoring.
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7 days
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Steady State Cmax of Mibefradil
Time Frame: daily for 7 days
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Pharmacokinetics assessments will include the determination of plasma concentrations of mibefradil and its major metabolite.
Blood samples will be drawn on Day 1: pre-dose 1, 30 minutes, 1 hr, 2 hr, 3 hr, 4 hr, pre-dose 2, pre-dose 3, pre-dose 4; Day 2: pre-dose 1, pre-dose 3; Day 3: pre-dose 1, pre-dose 3; Day 4: pre-dose 1, 30 minutes, 1 hr, 2 hr, 3 hr, 4 hr, pre-dose 2, pre-dose 3; Day 5: pre-dose 1, pre-dose 3; Day 6: pre-dose 1, pre-dose 3; and Day 7: pre-dose 1, pre-dose 3, pre-dose 4, 30 minutes, 1 hr, 2 hr, 3 hr, 4 hr, 5 hr, 7 hr, 9 hr after dosing.
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daily for 7 days
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Half Life of Mibefradil
Time Frame: daily for 7 days
|
Pharmacokinetics assessments will include the determination of plasma concentrations of mibefradil and its major metabolite.
Blood samples will be drawn on Day 1: pre-dose 1, 30 minutes, 1 hr, 2 hr, 3 hr, 4 hr, pre-dose 2, pre-dose 3, pre-dose 4; Day 2: pre-dose 1, pre-dose 3; Day 3: pre-dose 1, pre-dose 3; Day 4: pre-dose 1, 30 minutes, 1 hr, 2 hr, 3 hr, 4 hr, pre-dose 2, pre-dose 3; Day 5: pre-dose 1, pre-dose 3; Day 6: pre-dose 1, pre-dose 3; and Day 7: pre-dose 1, pre-dose 3, pre-dose 4, 30 minutes, 1 hr, 2 hr, 3 hr, 4 hr, 5 hr, 7 hr, 9 hr after dosing.
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daily for 7 days
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antihypertensive Agents
- Vasodilator Agents
- Enzyme Inhibitors
- Membrane Transport Modulators
- Cytochrome P-450 Enzyme Inhibitors
- Calcium-Regulating Hormones and Agents
- Calcium Channel Blockers
- Cytochrome P-450 CYP1A2 Inhibitors
- Mibefradil
Other Study ID Numbers
- TAU-2011-01
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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