A Phase I, Randomized, Double-blind, Placebo-controlled, Rising-dose Study to Assess the Tolerability, Safety, Pharmacokinetics, and Pharmacodynamics of Single IV Doses of AR09 in Healthy Subjects
Overview
- Phase
- Phase 1
- Intervention
- AR09 solution
- Conditions
- Anesthesia
- Sponsor
- Arbor Pharmaceuticals, Inc.
- Enrollment
- 17
- Locations
- 1
- Primary Endpoint
- Determine the maximum tolerated dose (MTD) of single IV doses of AR09
- Status
- Terminated
- Last Updated
- 4 years ago
Overview
Brief Summary
This will be a randomized, double-blind, placebo-controlled, rising-dose study of single IV doses of AR09 in healthy subjects. Each infusion will occur over 10 minutes.
Detailed Description
Each subject will complete Screening, Baseline, Treatment, and Follow-Up Phases. The Screening Phase will be conducted on an outpatient basis within 30 days, but no less than 3 days, prior to the start of the Baseline Phase. The Baseline Phase will consist of clinical research unit (CRU) admission and final qualification assessments. The Treatment Phase will be comprised of dosing on Day 1, post-treatment safety and pharmacodynamic assessments, and blood and urine collection. Subjects may be discharged approximately 24 hours after study drug administration on Day 2, provided the Modified Aldrete Score and all designated discharge criteria are clinically acceptable to the Investigator. The Follow-Up Phase will occur on Study Day 5 (± 1 day).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Males/females between 18 to 50 years of age, inclusive;
- •Body mass index 18 to 30 kg/m2, inclusive.
- •All females must have a negative serum beta human chorionic gonadotropin test result at screening and a negative urine pregnancy test result at baseline. Female subjects must be either post-menopausal, surgically sterile or using an acceptable method of contraception. Acceptable surgical sterilization techniques are hysterectomy, bilateral tubal ligation with surgery at least 6 months prior to dosing and bilateral oophorectomy with surgery at least 2 months prior to dosing. Acceptable methods of contraception are an intrauterine device, contraceptive implant, oral contraceptive (stable dose of the same hormonal contraceptive product for at least 12 weeks prior to dosing), a vasectomized partner and a double-barrier method (condom + spermicide / diaphragm + spermicide).
- •Willing and able to provide voluntary, written informed consent.
Exclusion Criteria
- •Acute illness within 2 weeks prior to dosing;
- •History of any chronic illness or evidence of significant organic or psychiatric disease on medical history or physical examination which, in the opinion of the Investigator would confound the study results or present a risk to the subject;
- •History of any clinically significant pulmonary conditions, within the last 2 years requiring admission to the hospital;
- •Spirometry forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) ratio less than 70%;
- •If female, pregnant or lactating;
- •Clinically significant illness or abnormality on physical examination, or ECG, including measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle (QTc interval) \>440 msec, on Screening or pre-dose 12-lead ECG;
- •Resting heart rate while awake \< 45 or \> 90 b/m;
- •Laboratory value(s) outside the laboratory reference range considered clinically significant (clinical chemistry, hematology, coagulation, ACTH, urinalysis, or pregnancy test).
- •Presence of type I or type II diabetes;
- •History of a severe allergic reaction to any drug or multiple food/drug allergies;
Arms & Interventions
AR09 solution
AR09, Randomized, Double-blind, Placebo-controlled, Rising-dose Study to Assess the Tolerability, Safety, Pharmacokinetics, and Pharmacodynamics of Single IV Doses of AR09 in Healthy Subjects
Intervention: AR09 solution
AR09 solution
AR09, Randomized, Double-blind, Placebo-controlled, Rising-dose Study to Assess the Tolerability, Safety, Pharmacokinetics, and Pharmacodynamics of Single IV Doses of AR09 in Healthy Subjects
Intervention: placebo
Placebo (for AR09 solution)
Placebo; normal saline
Intervention: AR09 solution
Placebo (for AR09 solution)
Placebo; normal saline
Intervention: placebo
Outcomes
Primary Outcomes
Determine the maximum tolerated dose (MTD) of single IV doses of AR09
Time Frame: 4 hours
Incidence of treatment-emergent adverse events (AE) by dose, including changes in temperature, respiratory rate, respiratory function at specified intervals post-dosing up to 24 hours. * Treatment-emergent changes in 12-lead electrocardiogram (ECG) recordings compared to pre-dose at specified intervals post-dosing and at Follow-Up including changes in heart rate and rhythm by dose at specified intervals post-dosing through 24 hours. * Treatment-emergent changes in group mean systolic and group mean diastolic blood pressure by dose at specified intervals post-dosing through 24 hours. * Treatment-emergent changes in clinical laboratory tests at specified intervals post-dosing and at Follow-Up. * Adrenocorticotropic hormone (ACTH) test to evaluate adrenal function pre and post dose.
Secondary Outcomes
- Characterize the single dose pharmacokinetics (PK) of IV doses of AR09 and its predominate metabolite, ADX892(24 hours)