Safety and Pharmacokinetics Study of CARD-024 in Healthy Subjects - Full Text View

Purpose

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

Condition	Intervention	Phase
Drug Safety Heart; Disease, Activity	Drug: CARD-024 Other: Drug Carrier	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	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

Resource links provided by NLM:

MedlinePlus related topics: Vitamin D

Drug Information available for: Vitamin D

U.S. FDA Resources

Further study details as provided by Cardiavent Inc.:

Primary Outcome Measures:

Safety [ Time Frame: 5 days ] [ Designated as safety issue: Yes ]
Adverse events such as nausea, vomiting, headache, muscle ache, neuralgia and patient overall tolerance to drug.

Secondary Outcome Measures:

Drug Pharmacokinetics [ Time Frame: 5 days ] [ Designated as safety issue: No ]
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.
Drug Pharmacodynamics [ Time Frame: 5 days ] [ Designated as safety issue: No ]
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.

Other Outcome Measures:

Induction of Hypercalcemia [ Time Frame: 5 days ] [ Designated as safety issue: Yes ]
Measure of serum calcium levels post treatment to assess drug calcemic activity.

Enrollment:	34
Study Start Date:	September 2011
Study Completion Date:	January 2012
Primary Completion Date:	December 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: CARD-024 CARD-024 oral administered: 3, 9, 27 or 81 mcg.	Drug: CARD-024 Comparison of different dosages of drug Other Name: 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 Name: Placebo, 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*

3 μg
9 μg
27 μg
81 μg

Eligibility

Ages Eligible for Study:	18 Years to 55 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Healthy males and females between the ages of 18 and 55, inclusive, with body mass index (BMI) between 18-32 kg/m2.
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.
No clinically significant findings on physical examination, including BP, pulse rate and 12-lead ECG. No clinically significant medical history.
No clinically significant safety laboratory results at Screening. Cardiavent, Inc. - CONFIDENTIAL
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.
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.
Willing and able to stay in the clinic for the inpatient activities required by the protocol for all visits.

Exclusion Criteria:

Evidence of clinically relevant pathology that could interfere with the study results or put the subject's safety at risk.
Current or recurrent disease that may affect the action, absorption, or disposition of the study treatment, or clinical or laboratory assessments.
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.
History of febrile illness within the 5 days prior to the first dose.
Positive Hepatitis B surface antigen (HbsAg), Hepatitis C antibody or Human Immunodeficiency Virus (HIV) test result at Screening visit.
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.
Use of any herbal supplements (including herbal weight-loss or "metabolism booster" therapies) within 30 days prior to the first dose of trial medication.
Known or suspected intolerance or hypersensitivity to similar study drugs or excipients, closely related compounds or any of their stated ingredients.
Positive screen for alcohol or drugs of abuse during Screening visit or at study check-in for Day 1 dosing.
Participated in a clinical study involving an investigational drug within 30 days or 5 half-lives (whichever is longer) prior to study drug administration.
Blood donation of 1 pint or more within 56 days of the start of the study.
Plasmapheresis or plasma donation within 30 days of the start of the study.
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.
Any condition that in the opinion of the Principal Investigator would complicate or compromise the study or the well-being of the subject.
Unwilling or unable to comply with the clinic house rules.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01757860

Locations

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

Sponsors and Collaborators

Cardiavent Inc.

Investigators

Principal Investigator:	James Vanderlugt, MD	Jasper Clinic, Michigan
Study Chair:	Robert U Simpson, PhD	Cardiavent Inc.

More Information

No publications provided

Responsible Party:	Cardiavent Inc.
ClinicalTrials.gov Identifier:	NCT01757860 History of Changes
Other Study ID Numbers:	CARD-024-C001
Study First Received:	December 17, 2012
Last Updated:	December 28, 2012
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Vitamin D
Vitamins
Bone Density Conservation Agents
Physiological Effects of Drugs

Pharmacologic Actions
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on May 21, 2013