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

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ClinicalTrials.gov Identifier: NCT02027155
Recruitment Status : Terminated (Study stopping criteria was met)
First Posted : January 6, 2014
Last Update Posted : March 15, 2016
Sponsor:
Information provided by (Responsible Party):
Arbor Pharmaceuticals, Inc.

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.

Condition or disease Intervention/treatment Phase
Anesthesia Drug: AR09 solution Drug: placebo Phase 1

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).

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 17 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Official Title: 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
Study Start Date : December 2013
Actual Primary Completion Date : April 2014
Actual Study Completion Date : April 2014

Arm Intervention/treatment
Active Comparator: 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
Drug: AR09 solution
moderate levels of sedation
Drug: placebo
Sterile Saline, USP
Other Name: Sterile Saline, United States Pharmacopeial (USP)
Placebo Comparator: Placebo (for AR09 solution)
Placebo; normal saline
Drug: AR09 solution
moderate levels of sedation
Drug: placebo
Sterile Saline, USP
Other Name: Sterile Saline, United States Pharmacopeial (USP)



Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. Characterize the single dose pharmacokinetics (PK) of IV doses of AR09 and its predominate metabolite, ADX892 [ Time Frame: 24 hours ]

    Individual and group plasma concentration-time curves of AR09 and ADX892 (metabolite);

    • Individual and group maximum concentration (Cmax) and time to observed peak plasma concentration (Tmax);
    • For AR09, individual and group estimates of area under the curve (AUC) AUC 0-t, AUC 0-∞, terminal phase rate constant (λz), t1/2, systemic clearance (CL), and volumes of distribution (Vz and Vss).
    • For ADX892, individual and group estimates of AUC 0-t, AUC 0-∞, terminal phase rate constant (λz), and t1/2. Additional PK parameters for the metabolite, such as metabolite to parent ratios will be calculated on the basis of the available data.
    • Compartmental pharmacokinetic analysis may be employed depending upon the appearance of the AR09 and ADX892 plasma concentration-time profiles.


Other Outcome Measures:
  1. Determine the safety and tolerability of single IV doses of AR09 [ Time Frame: 24 hours ]
    Incidence of treatment-emergent adverse events (AE) by dose.

  2. Identify doses of AR09 which produce moderate levels of sedation. [ Time Frame: 4 hours ]
    • Mean Bispectral (BIS) index by dose at specified intervals post-dosing
    • Mean Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score by dose at specified intervals post-dosing
    • Minute volume (tidal volume x respiratory rate)
    • End-tidal carbon dioxide (CO2) capnography by dose at specified intervals post-dosing
    • iPad-based cognitive tests by dose at specified intervals post-dosing



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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;
  • Subjects with a formal diagnosis obstructive sleep apnea or having a score of >3 on the STOP-Bang questionnaire (see Appendix 4);
  • Reported chronic (regular use for >1 month) use of medication of any kind (except contraceptives as described in the inclusion criteria), unless approved by the Sponsor;
  • 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;
  • Consumption of alcohol within 72 hours prior to dosing, or a positive qualitative urine drug or cotinine screen, or positive oral screen for the presence of alcohol;
  • Consumption of herbal supplements, grapefruit or grapefruit juice within 14 days before dosing;
  • Blood donation of approximately 400 mL or more within 4 weeks or plasma donation within 2 weeks prior to dosing;
  • Received an investigational product within 30 days of first dose in this study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02027155


Locations
United States, North Carolina
Duke Clinical Research Unit
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Arbor Pharmaceuticals, Inc.
Investigators
Principal Investigator: David MacLeod, MD Duke University

Responsible Party: Arbor Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02027155     History of Changes
Other Study ID Numbers: AR09.001
AR09.001 ( Other Identifier: IND )
First Posted: January 6, 2014    Key Record Dates
Last Update Posted: March 15, 2016
Last Verified: August 2015

Keywords provided by Arbor Pharmaceuticals, Inc.:
healthy volunteers

Additional relevant MeSH terms:
Pharmaceutical Solutions