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

NCT01550458 | Completed Phase 1

• 1 other identifier: TAU-2011-01
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Keywords

Clinical Trial, Phase I; Human Volunteers; Healthy Volunteers; mibefradil; Posicor®

Outcome Measures

Primary Outcomes (1)

• Determine the safety of a 7-day course of oral mibefradil in four divided daily doses in normal healthy volunteers.

  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.

  7 days

Secondary Outcomes (2)

• Steady State Cmax of Mibefradil

  daily for 7 days

• Half Life of Mibefradil

  daily for 7 days

Study Arms (2)

Mibefradil

EXPERIMENTAL

Drug: mibefradil

Placebo

PLACEBO COMPARATOR

Other: Placebo

Interventions

mibefradil 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.

Also known as: Posicor®, mibefradil dihyrdochloride, RO 40-5967

Mibefradil

Placebo OTHER

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

Also known as: sugar pill

Placebo

Eligibility Criteria

• Age: 19 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Cavion, Inc.: lead
• Celerion: collaborator
• Dana-Farber Cancer Institute: collaborator
• LifeWatch Services, Inc.: collaborator

Study Sites (1)

Celerion, Inc.

Lincoln, Nebraska, 68502, United States

Location

MeSH Terms

Interventions

Mibefradil; Sugars

Intervention Hierarchy (Ancestors)

Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Polycyclic Compounds; Carbohydrates

Study Officials

• Scott Rasmussen, MD

  Celerion

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 29, 2012
• First Posted: March 12, 2012
• Study Start: February 1, 2012
• Primary Completion: June 24, 2012
• Study Completion: June 24, 2012
• Last Updated: April 8, 2019

Record last verified: 2018-01

Locations

US (1)