Phase I Rising-dose Study to Assess Tolerability, Safety, Pharmacokinetics, Pharmacodynamics of AR09

NCT02027155 | Terminated Phase 1 DMC

• 1 other identifier: AR09.001
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

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.

Conditions

Anesthesia

Keywords

healthy volunteers

Outcome Measures

Primary Outcomes (1)

• Determine the maximum tolerated dose (MTD) of single IV doses of AR09

  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.

  4 hours

Secondary Outcomes (1)

• Characterize the single dose pharmacokinetics (PK) of IV doses of AR09 and its predominate metabolite, ADX892

  24 hours

Other Outcomes (2)

• Determine the safety and tolerability of single IV doses of AR09

  24 hours

• Identify doses of AR09 which produce moderate levels of sedation.

  4 hours

Study Arms (2)

AR09 solution

ACTIVE COMPARATOR

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

Drug: AR09 solution; Drug: placebo

Placebo (for AR09 solution)

PLACEBO COMPARATOR

Placebo; normal saline

Drug: AR09 solution; Drug: placebo

Interventions

AR09 solution DRUG

moderate levels of sedation

Also known as: investigational product

AR09 solution; Placebo (for AR09 solution)

placebo DRUG

Sterile Saline, USP

Also known as: Sterile Saline, United States Pharmacopeial (USP)

AR09 solution; Placebo (for AR09 solution)

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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;
• Subjects with a formal diagnosis obstructive sleep apnea or having a score of \>3 on the STOP-Bang questionnaire (see Appendix 4);
• Reported use of any prescription drug within 14 days prior to dosing, any non-prescription drug or vitamin within 7 days prior to dosing, any known enzyme-inducer, enzyme-inhibitor, or other investigational drug within 30 days prior to dosing, or reported chronic exposure to enzyme-inducers such as paint solvents or pesticides within 30 days of dosing, unless approved by the Sponsor; hormonal contraceptive will be permitted if the subject has been using it for at least 12 weeks prior to dosing;
• History of alcohol or illicit drug abuse within the past two years, or current reported average alcohol intake \> two alcoholic drinks per day (e.g., more than 24 oz. of beer, 10 oz. of wine, or 3 oz. of hard liquor);
• Regular use of tobacco or nicotine containing products within 1 year of study entry;
• Average consumption of ≥ 6 caffeine containing beverages per day;

Sponsors & Collaborators

• Arbor Pharmaceuticals, Inc.: lead

Study Sites (1)

Duke Clinical Research Unit

Durham, North Carolina, 27710, United States

Location

Study Officials

• David MacLeod, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: December 29, 2013
• First Posted: January 6, 2014
• Study Start: December 1, 2013
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: April 13, 2022

Record last verified: 2022-04

Locations

US (1)