Safety and Pharmacokinetics Study of CARD-024 in Healthy Subjects (CARD-024)

A Randomized, Double-Blind, Placebo-Controlled, Ascending Single-Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of CARD-024 (1α-Hydroxy-Vitamin-D5) in Healthy Subjects

Study Phase: Phase 1

Primary Objective:

• To evaluate the safety and tolerability of single ascending oral doses of CARD-024 in healthy subjects

Secondary Objectives:

• To evaluate the pharmacokinetic (PK) profile of CARD-024 following ascending single oral doses of CARD-024
• To evaluate the effect of CARD-024 on cardiovascular indices including plasma renin activity (PRA) and blood pressure (BP), biological markers of activity, following ascending single oral doses of CARD-024

Study Overview

• Status: Completed
• Conditions: Drug Safety; Heart; Disease, Activity
• Intervention / Treatment: Drug: CARD-024; Other: Drug Carrier

Detailed Description

Study Design: This is a single-center, double-blind, randomized, placebo-controlled study of single oral doses of CARD-024. Four planned cohorts of 8 subjects each will be dosed sequentially and randomized to receive a single dose of active drug (6 subjects) or placebo (2 subjects). Cohort 4 will have 10 subjects randomized to receive active drug (7 subjects) or placebo (3 subjects). Each cohort will be divided into at least 2 groups; the first group will have 2 subjects, 1 receiving active drug and 1 receiving placebo. Dosing of the remaining 6 subjects in each cohort will be completed in a manner agreed upon by the Sponsor and the Principal Investigator in keeping with the randomization schedule and blinded conditions.

The planned cohorts are:

Cohort CARD-024 Dose*

1. 3 μg
2. 9 μg
3. 27 μg
4. 81 μg

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Kalamazoo, Michigan, United States, 49007
      • Jasper Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy males and females between the ages of 18 and 55, inclusive, with body mass index (BMI) between 18-32 kg/m2.
2. Females must be surgically sterile or at least 2 years post-menopausal. Menopausal status will be verified by a follicular stimulating hormone (FSH) test. Those with bilateral tubal ligation must also use a barrier method of birth control. In addition, all females must have a negative pregnancy test at Screening.
3. No clinically significant findings on physical examination, including BP, pulse rate and 12-lead ECG. No clinically significant medical history.
4. No clinically significant safety laboratory results at Screening. Cardiavent, Inc. - CONFIDENTIAL
5. Nonsmoker or light smoker (≤5 cigarettes per day or similar use of other tobacco products) and are willing to refrain from smoking while in the clinic.
6. Willing and able to sign an informed consent document indicating understanding the purpose of and procedures required for the study and willingness to participate in the study.
7. Willing and able to stay in the clinic for the inpatient activities required by the protocol for all visits.

Exclusion Criteria:

1. Evidence of clinically relevant pathology that could interfere with the study results or put the subject's safety at risk.
2. Current or recurrent disease that may affect the action, absorption, or disposition of the study treatment, or clinical or laboratory assessments.
3. Current or relevant previous history of serious, severe, or unstable (acute or progressive) physical or psychiatric illness, any medical disorder requiring treatment or that may make the subject unlikely to fully complete the study, or any condition that presents undue risk from the study treatment or procedures.
4. History of febrile illness within the 5 days prior to the first dose.
5. Positive Hepatitis B surface antigen (HbsAg), Hepatitis C antibody or Human Immunodeficiency Virus (HIV) test result at Screening visit.
6. Use of any prescription medication or over-the-counter (OTC) medication within 7 days or 5 half-lives (whichever is longer) prior to the first dose of trial medication or during the study. As an exception, acetaminophen may be used at doses up to 1 g/day.
7. Use of any herbal supplements (including herbal weight-loss or "metabolism booster" therapies) within 30 days prior to the first dose of trial medication.
8. Known or suspected intolerance or hypersensitivity to similar study drugs or excipients, closely related compounds or any of their stated ingredients.
9. Positive screen for alcohol or drugs of abuse during Screening visit or at study check-in for Day 1 dosing.
10. Participated in a clinical study involving an investigational drug within 30 days or 5 half-lives (whichever is longer) prior to study drug administration.
11. Blood donation of 1 pint or more within 56 days of the start of the study.
12. Plasmapheresis or plasma donation within 30 days of the start of the study.
13. Single 12-lead ECG demonstrating QTc >450 msec at Screening, and or history or evidence of long QT syndrome. A single repeat ECG may be done at the Principal Investigator's discretion.
14. Any condition that in the opinion of the Principal Investigator would complicate or compromise the study or the well-being of the subject.
15. Unwilling or unable to comply with the clinic house rules.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: CARD-024; CARD-024 oral administered: 3, 9, 27 or 81 mcg.	Drug: CARD-024; Comparison of different dosages of drug; Other Names: 1α-Hydroxy-Vitamin-D5; 1αVitD5
PLACEBO_COMPARATOR: Drug Carrier; Placebo: 20% ethanol:80% propylene glycol solution oral administered.	Other: Drug Carrier; Drug Carrier, 20% ethanol:80% propylene glycol oral administered solution.; Other Names: Placebo, Drug Carrier

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety	Adverse events such as nausea, vomiting, headache, muscle ache, neuralgia and patient overall tolerance to drug.	5 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Drug Pharmacokinetics	Measure of drug absorption and elimination by measuring drug blood levels after oral administration. Assessment of drug C-max, T-lag, T-1/2, AUC, Vd/F and K-a.	5 days
Drug Pharmacodynamics	Measure of pharmacodynamics by 1] measuring plasma renin activity (PRA), 2] measuring plasma parathyroid hormone (PTH) levels, and 3] measuring drug effect on systolic and diastolic blood pressure by arm cuff occlusion.	5 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Induction of Hypercalcemia	Measure of serum calcium levels post treatment to assess drug calcemic activity.	5 days

Collaborators and Investigators

• Sponsor: Cardiavent Inc.
• Investigators: Study Chair: Robert U Simpson, PhD, Cardiavent Inc.

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (ACTUAL): December 1, 2011
• Study Completion (ACTUAL): January 1, 2012

Study Registration Dates

• First Submitted: December 17, 2012
• First Submitted That Met QC Criteria: December 28, 2012
• First Posted (ESTIMATE): December 31, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): December 31, 2012
• Last Update Submitted That Met QC Criteria: December 28, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Vitamin D
• Other Study ID Numbers: CARD-024-C001