Study for Naltrexone on the Abuse Potential of Methylphenidate

NCT03769064 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: AVK-001
• Study Type: interventional
• Target: 94
• Locations: 1 country
• Sites: 1

Brief Summary

The current abuse liability study aims to assess the potential for co-administration of naltrexone (NTX) to reduce the abuse potential of methylphenidate (MPH).

Conditions

Naltrexone; Methylphenidate Abuse

Keywords

ADHD; attention deficit hyperactivity disorder; stimulant

Outcome Measures

Primary Outcomes (1)

• Maximum Effect of Naltrexone

  To evaluate the maximum effect of 2 doses (50 and 100 mg) of Naltrexone on the abuse potential of a single dose (60 mg) of Methylphenidate in healthy recreational stimulant users using the bipolar Visual Analogue Scale for Drug Liking. Visual Analogue Scale (bipolar) is an administered test where the patient assess the following.: • Drug Liking, Overall Drug Liking, Alertness/Drowsiness, Overall Take the Drug Again; The response anchors are 0 (strong disliking), 50 (neither like nor dislike), and 100 (strong liking). Visual Analogue Scale for Drug Liking will be determined periodically over the 8 hour period following each dose administration to assess for response to test question, "At this moment, my liking for this drug is...".

  70 days

Secondary Outcomes (16)

• Time to Maximum Effect of Naltrexone

  70 days

• Effect of Naltrexone

  70 days

• Time to Minimum Effect

  70 days

• Time-Average Area Under the Effect Curve

  70 days

• Adverse Events

  70 days

Study Arms (6)

Qualification Phase (Part A)

EXPERIMENTAL

Placebo/Methylphenidate (60 mg) on days 1 and 3

Drug: Placebo; Drug: Methylphenidate 60 mg

Qualification Phase (Part B)

EXPERIMENTAL

Methylphenidate (60 mg)/Placebo on days 1 and 3

Drug: Placebo; Drug: Methylphenidate 60 mg

Treatment Phase Sequence 4213

EXPERIMENTAL

Methylphenidate 60 mg/Naltrexone 100 mg Methylphenidate 60 mg/Placebo Placebo/Placebo Methylphenidate 60 mg/Naltrexone 50 mg

Drug: Treatment Phase Sequence 4213

Treatment Phase Sequence 2134

EXPERIMENTAL

Methylphenidate 60 mg/Placebo Placebo/Placebo Methylphenidate 60 mg/Naltrexone 50 mg Methylphenidate 60 mg/Naltrexone 100 mg

Drug: Treatment Phase Sequence 2134

Treatment Phase Sequence 1342

EXPERIMENTAL

Placebo/Placebo Methylphenidate 60 mg/Naltrexone 50 mg Methylphenidate 60 mg/Naltrexone 100 mg Methylphenidate 60 mg/Placebo

Drug: Treatment Phase Sequence 1342

Treatment Phase Sequence 3421

EXPERIMENTAL

Methylphenidate 60 mg/Naltrexone 50 mg Methylphenidate 60 mg/Naltrexone 100 mg Methylphenidate 60 mg/Placebo Placebo/Placebo

Drug: Treatment Phase Sequence 3421

Interventions

Placebo DRUG

Potential subjects will be screened to determine their eligibility for the study within 28 days of the first dose in the Qualification Phase (i.e., Days -28 to -2). Eligible subjects will be admitted to the clinical site on Day -1 of the Qualification Phase (Part 1) and randomized on Day 1 to receive placebo and MPH (60 mg) in 1 of 2 sequences with a 48-hour washout between dose administrations (i.e., dose administration on Days 1 and 3).

Also known as: Qualification Phase (Part A)

Qualification Phase (Part A); Qualification Phase (Part B)

Methylphenidate 60 mg DRUG

Potential subjects will be screened to determine their eligibility for the study within 28 days of the first dose in the Qualification Phase (i.e., Days -28 to -2). Eligible subjects will be admitted to the clinical site on Day -1 of the Qualification Phase (Part 1) and randomized on Day 1 to receive placebo and MPH (60 mg) in 1 of 2 sequences with a 48-hour washout between dose administrations (i.e., dose administration on Days 1 and 3).

Also known as: Qualification Phase (Part A)

Qualification Phase (Part A); Qualification Phase (Part B)

Treatment Phase Sequence 4213 DRUG

Subjects will be administered single doses on Days 1, 4, 7, and 10 of the Treatment Phase.

Also known as: Treatment 1

Treatment Phase Sequence 4213

Treatment Phase Sequence 2134 DRUG

Subjects will be administered single doses on Days 1, 4, 7, and 10 of the Treatment Phase.

Also known as: Treatment 2

Treatment Phase Sequence 2134

Treatment Phase Sequence 1342 DRUG

Subjects will be administered single doses on Days 1, 4, 7, and 10 of the Treatment Phase.

Also known as: Treatment 3

Treatment Phase Sequence 1342

Treatment Phase Sequence 3421 DRUG

Subjects will be administered single doses on Days 1, 4, 7, and 10 of the Treatment Phase.

Also known as: Treatment 4

Treatment Phase Sequence 3421

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Recreational stimulant users, defined as ≥10 lifetime non-therapeutic experiences (i.e., for psychoactive effects) with CNS stimulants (e.g., amphetamines, cocaine, MPH) and ≥1 non-therapeutic use of a CNS stimulant within the 12 weeks prior to Screening.
• A body mass index of ≥18 to ≤34 kg/m2 at Screening.
• In good health, as determined by medical history, PE, vital signs assessments, 12-lead ECG, and clinical laboratory evaluations.
• A female study subject must meet one of the following criteria:
• If of childbearing potential - is abstinent from heterosexual intercourse or uses 2 of the accepted contraceptive regimens from at least 30 days prior to the first administration of the study medication, during the study, and for at least 30 days after the last dose of the study medication. An acceptable method of contraception includes the following:
• Progestogen-containing hormonal contraceptives (birth control pills, injectable/implantable/insertable hormonal birth control products, transdermal patch) and use of condom with spermicide
• Intrauterine device (without hormones)
• Condom
• Spermicide
• If of non-childbearing potential - should be surgically sterile (i.e. has undergone complete hysterectomy, bilateral oophorectomy, or tubal ligation) or in a menopausal state (at least 1 year without menses), as confirmed by follicle-stimulating hormone (FSH) levels (postmenopausal must be confirmed by the subject having a serum FSH greater than 40 mIU/mL at Screening). Females of non-childbearing potential must present a proof of postmenopausal status and/or partial or total hysterectomy; if such proof is not available, the female will be considered to be of childbearing potential.
• A male study subject must agree to use one of the accepted contraceptive regimens during the study and for at least 90 days after the last dose of the study medication:
• Abstinence from heterosexual intercourse
• Female partner use of hormonal contraceptives (birth control pills, injectable/implantable/insertable hormonal birth control products, transdermal patch)
• Female partner with intrauterine device (with or without hormones)
• Female partner with condom with spermicide used by male study subject

You may not qualify if:

• Evidence of moderate or severe substance use disorder (excluding nicotine and/or caffeine) within the past 2 years, as defined by the DSM-V, or has a lifetime history of participation in a drug rehabilitation program (excluding past participation in tobacco smoking cessation program or previous court-mandated treatment).
• History of opioid dependence.
• Abnormal pulse rate, blood pressure, oral body temperature, or respiration rate at Screening and prior to administration of any study drug that, in the opinion of the Investigator, increases the risk to the subject of participation in the study. For these parameters, out-of-range values that are not clinically significant (as determined by the Investigator) may be repeated twice and the subject may be enrolled if at least 1 repeated value is within acceptable range.
• Abnormal 12-lead ECG at Screening and prior to first dose of any study drug that, in the opinion of the Investigator, increases the risk to the subject of participation in the study.
• Any clinically significant medical history that, in the opinion of the Investigator, increases the risk to the subject of participation in the study.
• A history of a major surgical procedure within 30 days prior to the start of study drug administration (Day 1 of Part 1), or any planned surgery during the study.
• A history of any clinically significant illness within 30 days of the start of study drug administration (Day 1 of Part 1), as determined by the Investigator.
• History of liver disease.
• History of narrow-angle glaucoma, based on medical history and/or subject self-reporting.
• Presence of galactose intolerance, lactase deficiency, or glucose-galactose malabsorption.
• Presence or history of any narrowing or blockage of the digestive system.
• Donation of blood, platelets, or plasma within 3 months prior to Screening.
• Presence or a history of any clinically significant neurological, gastrointestinal, renal, hepatic, cardiovascular, psychiatric, respiratory, metabolic, endocrine, hematological, or other major disorders (including a history of angioedema), as determined by the Investigator.
• A family history of sudden death or sudden cardiac arrest, as determined by the Investigator.
• Presence or history of any medically diagnosed, clinically significant Axis I psychiatric disorder (including bipolar disorder, mood disorder, anxiety disorder, thought disorder, any psychotic disorder).

Sponsors & Collaborators

• Avekshan LLC: lead

Study Sites (1)

Vince & Associates Clinical Research, Inc.

Overland Park, Kansas, 66212, United States

Location

MeSH Terms

Conditions

Attention Deficit Disorder with Hyperactivity

Interventions

Methylphenidate

Condition Hierarchy (Ancestors)

Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Pradeep Bhide, PhD

  Co-Founder and Chief Scientist

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double-blind, randomized
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study will consist of a 2-period crossover Qualification Phase (Part 1) to ensure subject eligibility for the treatment phase of the study, and a 4-period crossover Treatment Phase (Part 2) to determine the effect of concomitant administration of MPH and NTX on subjective pharmacodynamic (PD) measures of abuse, relative to MPH and placebo.

Study Record Dates

• First Submitted: October 11, 2018
• First Posted: December 7, 2018
• Study Start: March 27, 2018
• Primary Completion: June 20, 2018
• Study Completion: June 20, 2018
• Last Updated: December 7, 2018

Record last verified: 2018-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)