Safety Study of Mibefradil When Given Four Times a Day in Healthy Volunteers

NCT ID: NCT01550458

Last Updated: 2019-04-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-02-29
• Study Completion Date: 2012-06-24

Brief Summary

The objective of the study is to determine the safety and pharmacokinetics of a 7 day course of oral mibefradil given four times a day in healthy volunteers. This is a dose escalation study in which the total daily dose of mibefradil will be increased with each cohort.

Detailed Description

This study will establish the safety, detailed pharmacokinetics, and, possibly, maximum tolerated dose (MTD) of ascending doses of mibefradil administered four times a day (QID) in healthy volunteers. The knowledge gained will then guide the details of a study of Interlaced Therapy™ in patients with recurrent High Grade Glioma (HGG). Non-clinical studies are currently on-going in the efficacy of Interlaced Therapy™ in ovarian cancer, pancreatic cancer, and intracranial malignancy.

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Mibefradil

Group Type: EXPERIMENTAL

mibefradil

Intervention Type: DRUG

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.

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

1 out of 6 patients per cohort will receive placebo tablets identical in appearance and number to the active mibefradil arm.

Interventions

mibefradil

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.

Intervention Type: DRUG

Placebo

1 out of 6 patients per cohort will receive placebo tablets identical in appearance and number to the active mibefradil arm.

Intervention Type: OTHER

Other Intervention Names

Posicor®; mibefradil dihyrdochloride; RO 40-5967; sugar pill

Eligibility Criteria

Inclusion Criteria

1. Normal healthy volunteers aged 19 to 55 years, male or female, and willing and able to sign informed consent;

2. 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.

3. Male subjects must continue to use their approved contraceptive method for 60 days after participating in the study.

4. Has a body mass index (BMI) between 18.0 and 32.0 kg/m², inclusive; and

5. Have no acute illnesses or chronic health issues that require medication.

Exclusion Criteria

1. History of investigational drug use within 30 days of this study;

2. 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;

3. History of hypertension, treated or untreated, or screening BP >140 mm Hg systolic or >90 mm Hg diastolic;

4. Currently or within the last 14 days taking any medications (prescription, nonprescription, or herbal or Chinese remedies) including oral contraceptives and hormone replacement therapy;

5. 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;

6. Current smoker (more than 10 cigarettes/day) for 6 months;

7. 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;

8. 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;

9. Subject, in the Investigator's opinion, is likely to have unrecognized cardiovascular disease, based on history or the presence of risk factors;

10. Subject is currently taking or had taken in the previous 14 days, herbal preparations containing St. John's Wort (Hypericum perforatum);

11. Subject has a history of allergic reactions to calcium channel antagonists;

12. 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;

13. 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);

14. Allergy to latex or rubber;

15. Hemoglobin under laboratory lower limit of normal; or

16. 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.

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Celerion

INDUSTRY

Sponsor Role: collaborator

Dana-Farber Cancer Institute

OTHER

Sponsor Role: collaborator

LifeWatch Services, Inc.

INDUSTRY

Sponsor Role: collaborator

Cavion, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Scott Rasmussen, MD

Role: PRINCIPAL_INVESTIGATOR

Celerion

Locations

Celerion, Inc.

Lincoln, Nebraska, United States

Countries

United States

Other Identifiers

TAU-2011-01

Identifier Type: -

Identifier Source: org_study_id