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OLANI PK/Safety Study in Healthy Volunteers

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ClinicalTrials.gov Identifier: NCT03810495
Recruitment Status : Recruiting
First Posted : January 18, 2019
Last Update Posted : April 18, 2019
Sponsor:
Collaborators:
National Institute on Drug Abuse (NIDA)
New York State Psychiatric Institute
Columbia University
Clinilabs, Inc.
Information provided by (Responsible Party):
Go Medical Industries Pty Ltd

Brief Summary:
This study will examine the pharmacokinetic profile and safety of the O'Neil Long Acting Naltrexone Implant (OLANI) overtime in healthy volunteers. All participants will be treated in an open label manner. No randomization will occur. It is hypothesized that the OLANI will provide sustained therapeutic doses of naltrexone (NTX) for periods up to 6 months via a single subcutaneous application of 2 OLANIs.

Condition or disease Intervention/treatment Phase
Opioid Use Disorder Drug: naltrexone implant Phase 1

Detailed Description:
Naltrexone (NTX) is a nonspecific pure opioid antagonist with a high affinity for the µ-opioid receptor. It blocks the effects of opioids by competitive binding at opiate receptors. NTX is used primarily in the management of opiate and alcohol dependence. It is available in the United States (US) as 2 formulations; a once daily oral formulation (Revia) and a once monthly intramuscular injection (Vivitrol). While NTX is a potent antagonist and efficiently blocks the effects of exogenous opiates such as heroin, the success of NTX for the treatment of opiate dependence has been limited by poor patient compliance. Therefore, the development of a sustained release NTX formulation (in excess of 1 month) would be of great benefit for the treatment of opioid use disorder.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: A Pilot Pharmacokinetic (PK) Trial of the O'Neil Long Acting Naltrexone Implant
Actual Study Start Date : April 11, 2019
Estimated Primary Completion Date : July 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: OLANI (naltrexone implant)
2 OLANI containing 60% naltrexone (1.8 g total) administered one time subcutaneously
Drug: naltrexone implant
1.8 g implant containing 60% naltrexone
Other Names:
  • OLANI
  • O'Neil Long Acting Naltrexone Implant




Primary Outcome Measures :
  1. Proportion of participants that maintain MEC [ Time Frame: up to 540 days or until NTX blood levels become undetectable ]
    Proportion of participants who maintain NTX blood levels of ≥1.33 ng/mL for ≥180 days


Secondary Outcome Measures :
  1. Mean Cmax of naltrexone [ Time Frame: pre-dose, at 3, 6, and 12 hours (± 60 minutes) after dosing; 24 and 48 hours (± 2 hours) after dosing; day 4 (± 1 day), day 8 (± 2 days); days 14, 21, 28, 35, 42, 49 and 56 (± 3 days); then every 30 days (± 10 days) up to 540 days ]
    Single-dose PK measurement of the plasma naltrexone concentration (Cmax) after dosing on Day 1

  2. Tmax of naltrexone [ Time Frame: pre-dose, at 3, 6, and 12 hours (± 60 minutes) after dosing; 24 and 48 hours (± 2 hours) after dosing; day 4 (± 1 day), day 8 (± 2 days); days 14, 21, 28, 35, 42, 49 and 56 (± 3 days); then every 30 days (± 10 days) up to 540 days ]
    Single-dose PK measurement of the time to reach the maximum (Tmax) naltrexone concentration after dosing on Day 1

  3. AUC of naltrexone [ Time Frame: pre-dose, at 3, 6, and 12 hours (± 60 minutes) after dosing; 24 and 48 hours (± 2 hours) after dosing; day 4 (± 1 day), day 8 (± 2 days); days 14, 21, 28, 35, 42, 49 and 56 (± 3 days); then every 30 days (± 10 days) up to 540 days ]
    Single-dose PK measurement of the area under the curve (AUC) for naltrexone after dosing on Day 1

  4. Time to undetectable naltrexone [ Time Frame: pre-dose, at 3, 6, and 12 hours (± 60 minutes) after dosing; 24 and 48 hours (± 2 hours) after dosing; day 4 (± 1 day), day 8 (± 2 days); days 14, 21, 28, 35, 42, 49 and 56 (± 3 days); then every 30 days (± 10 days) up to 540 days ]
    Mean time (T) to undetectable naltrexone blood levels

  5. Mean Cmax of 6β-naltrexol [ Time Frame: pre-dose, at 3, 6, and 12 hours (± 60 minutes) after dosing; 24 and 48 hours (± 2 hours) after dosing; day 4 (± 1 day), day 8 (± 2 days); days 14, 21, 28, 35, 42, 49 and 56 (± 3 days); then every 30 days (± 10 days) up to 540 days ]
    Single-dose PK measurement of the peak plasma 6β-naltrexol concentration after dosing on Day 1

  6. Mean Tmax of 6β-naltrexol [ Time Frame: pre-dose, at 3, 6, and 12 hours (± 60 minutes) after dosing; 24 and 48 hours (± 2 hours) after dosing; day 4 (± 1 day), day 8 (± 2 days); days 14, 21, 28, 35, 42, 49 and 56 (± 3 days); then every 30 days (± 10 days) up to 540 days ]
    Single-dose PK measurement of the time to reach the maximum 6β-naltrexol concentration after dosing on Day 1

  7. Time>Minimum Effective Concentration [ Time Frame: ppre-dose, at 3, 6, and 12 hours (± 60 minutes) after dosing; 24 and 48 hours (± 2 hours) after dosing; day 4 (± 1 day), day 8 (± 2 days); days 14, 21, 28, 35, 42, 49 and 56 (± 3 days); then every 30 days (± 10 days) up to 540 days ]
    Time (T) naltrexone remains above the minimum effective concentration (MEC) of 1.33

  8. AUC of 6β-naltrexol [ Time Frame: pre-dose, at 3, 6, and 12 hours (± 60 minutes) after dosing; 24 and 48 hours (± 2 hours) after dosing; day 4 (± 1 day), day 8 (± 2 days); days 14, 21, 28, 35, 42, 49 and 56 (± 3 days); then every 30 days (± 10 days) up to 540 days ]
    Single-dose PK measurement of the AUC for 6β-naltrexol concentration after dosing on Day 1

  9. Incidence of Adverse Events (AEs) [ Time Frame: Up to 540 days or until NTX blood levels become undetectable ]
    Incidence and Severity of AEs



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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Men or women between the ages of 18 and 55 years old (inclusive)
  • Without DSM 5 (The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition ) - Substance Related Disorders classification; in sustained remission is not exclusionary
  • Able and willing to comply with the requirements of the protocol
  • Able and willing to provide written informed consent
  • Willing to undergo a minor surgical procedure under local anesthetic to allow for investigational drug administration in the subcutaneous tissue
  • BMI inclusive of 18.5 to 30.0
  • Have an initial weight between 45.3 and 81.6 kilograms (inclusive)

Exclusion Criteria:

  • Positive urine drug screen (UDS) at screening for illicit substances.
  • Is currently on naltrexone medication.
  • Has had a naltrexone implant in the past 24 months.
  • Has received treatment with an extended naltrexone product (e.g. Vivitrol) in the past 12 months.
  • Has a condition which requires treatment with opioid based medication.
  • Has a known hypersensitivity to naltrexone.
  • Has a known hypersensitivity to poly-lactic based materials e.g. biodegradable sutures, surgical implants or previous biodegradable implants.
  • Has a known hypersensitivity to local anesthesia.
  • Is prone to skin rashes, irritation or has a skin condition such as recurrent eczema that is likely to impact the implant site area, or as determined by the evaluating physician.
  • Demonstrates any abnormal skin tissue in the proposed implantation area.
  • Is pregnant or planning to be. Women need to have negative blood pregnancy test at screening. Women need to agree to practice dual contraceptives.
  • Participant is breastfeeding or planning to be.
  • Has a current significant neurological (including cognitive and psychiatric disorders), hepatic, renal, endocrine, cardiovascular, gastrointestinal, pulmonary, hematological or metabolic disease unless currently controlled and stable with protocol-allowed medication 30 days prior to proposed investigational product administration.
  • Any clinically important abnormal finding as determined by medical history, physical examination, ECG or clinical laboratory tests.
  • Any additional condition(s) that in the investigator's opinion would prohibit the participant from completing the study or would not be in the best interest of the participant.
  • Alanine aminotransferase (ALT) or aspartate transaminase (AST) > 3 times the upper end of the laboratory normal range.
  • Any methadone use 14 days prior to screening, and up to Study Day 0.
  • Current DSM-5 diagnosis of schizophrenia, bipolar, anxiety, or depressive disorder, confirmed by the MINI diagnostic interview assessment, or currently treated with medications for anxiety or depression. Past history (in remission DSM-5 classification) of anxiety or depression is not exclusionary.
  • Any elevated risk for suicide measured using the Columbia Suicide Severity Rating Scale, endorsing any of the items in the past month (C-SSRS, Lifetime)
  • Is participating or intending to participate in any other clinical trial during the duration of 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): NCT03810495


Locations
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United States, New York
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Contact: Kaitlyn Mishlen, MA    646-774-6174    Kaitlyn.Mishlen@nyspi.columbia.edu   
Principal Investigator: Adam Bisaga, MD         
Sub-Investigator: Christine Rohde, MD         
Sponsors and Collaborators
Go Medical Industries Pty Ltd
National Institute on Drug Abuse (NIDA)
New York State Psychiatric Institute
Columbia University
Clinilabs, Inc.
Investigators
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Principal Investigator: Adam Bisaga, MD New York State Psychiatric Institute

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Responsible Party: Go Medical Industries Pty Ltd
ClinicalTrials.gov Identifier: NCT03810495     History of Changes
Other Study ID Numbers: GM0017
UG3DA047720 ( U.S. NIH Grant/Contract )
First Posted: January 18, 2019    Key Record Dates
Last Update Posted: April 18, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Go Medical Industries Pty Ltd:
naltrexone
opioids
opioid use disorder
OLANI implant
Additional relevant MeSH terms:
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Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Naltrexone
Alcohol Deterrents
Narcotic Antagonists
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents