- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04232644
Pilot Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Abuse Liability of an Abuse-Deterrent Immediate-Release Formulation (ADAIR)
A Pilot, Randomized, Double-Blind, Active-Controlled, 2-Treatment, Crossover Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Abuse Liability of Dextroamphetamine Sulfate From an Abuse-Deterrent Immediate-Release Formulation (ADAIR)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
VAL-103 is a phase 1, pilot, randomized, double-blind, active-controlled, 2-treatment crossover study. The study objectives include assessing the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of manipulated ADAIR 30 mg compared to crushed d-amphetamine sulfate IR 30 mg (DEX) administered IN in non-dependent recreational stimulant users. The primary PD endpoint is mean maximum drug liking (Emax) on a bipolar 100mm visual analog scale.
A total of 16 qualified subjects demonstrating a confirmed positive response to stimulants will enter the treatment phase. Safety will be assessed via adverse events, vital signs, ECGs, clinical laboratory tests, and Columbia Suicide Severity Rating Scale (C-SSRS).
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Ontario
-
Toronto, Ontario, Canada, M9L 3A2
- BioPharma Services Inc.
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- BMI within 18.5-32.0 kg/m2 and min weight of 50.0 kg
- healthy, according to med history, ECG, vital signs, lab results and physical exam
- clinical lab values within acceptable lab test range, unless otherwise deemed acceptable by PI
- SBP between 95-140 mmHg and DBP between 55-90 mmHg and HR between 50-100 bpm unless deemed not clinically significant by PI
- current or history of stimulant use for recreational purposes at least 10 times in lifetime and used stimulants at least once in the 12 weeks before screening
- experience with intranasal drug use for the purpose of recreational use on at least 3 occasions in the year prior to Screening
- ability to fast for at least 12 hours and consume standard meals
- agree not to have tattoo or body piercing until end of study
- female subject must be non-pregnant and non-lactating and fulfill at least one of following: participant is of childbearing potential and had used one of accepted contraception regimens from at least 30 days prior to first study drug and agrees to use two acceptable contraceptive regiment through at least 30 days after last dose of study drug or participant is of non-childbearing potential, defined as surgically sterile or is in a postmenopausal state
- a male subject must have met one of the following: participant is able to procreate and agreed to use one of accepted contraceptive regimens and not donate sperm from first study drug administration to at least 90 days after last drug administration or participant is unable to procreate, defined as surgically sterile and agreed to use a male condom from first study drug administration to at least 90 days after last drug administration
Exclusion Criteria:
- substance or alcohol dependence within the past 2 years
- history or presence of clinically significant abnormality as assessed by physical exam, med history, ECGs, vital signs, or lab results which in the opinion of the investigator would jeopardize the safety or the subject or validity of the study results
- history or presence of cardiovascular disorder, pre-existing structural cardiac abnormalities or other serious cardiac problems, prolonged QT syndrome, and associated risk factors
- abnormalities in the intranasal cavity or any condition that in the opinion of the PI would interfere with study procedures, data integrity, or compromise the safety of the subjects
- history or presence of mechanical gastrointestinal obstruction or any disease/conditions that affect bowel transit
- documented history of, or currently active, seizure disorder or history of clinically significant head injury or syncope of unknown origin
- history or presence of any psychiatric or neurological condition that, in the opinion of the PI, could get exacerbated by study drug exposure or interfere with study procedures
- subject with history of suicidal ideation or suicidal behavior as assessed by the Columbia Suicide Severity Rating Scale
- heavy smoker (>20 cigarettes per day) and/or is unable to abstain from smoking for a least 6 hours during the in-clinic periods
- history of severe allergic reaction to any substance, severe bronchial asthma, chronic obstructive airway, or previous status asthmaticus
- history of allergy or hypersensitivity to amphetamine salts, its excipients, or related substances
- history of food allergies, including lactose, and/or presence of any dietary restrictions
- positive test results for any of the following: HIV, Hep B, Hep C, positive drug screen at admission to the Qualification Phase or Treatment Phase, breath alcohol test and positive pregnancy test for females
- evidence of clinically significant hepatic or renal impairment including ALT or AST>1.5x the upper limit of normal (ULN) or bilirubin >1xULN
- known history or presence of: seizures or risk of seizure; tics or Tourette's Syndrome; psychosis, mania, bipolar disorder, suicidality or violent behavior; hyperthyroidism; Raynaud's Phenomenon; eye disorders
- individuals who have donated 50-499 mL of blood in the previous 30 days; or 500 mL or more in the previous 56 days
- donation of plasma by plasmapheresis within 7 days prior to first study drug administration
- difficulty with venous access or unsuitable or unwilling to undergo catheter insertion
- treatment with investigational drug within 5 times the elimination half-life, if known, or within 30 days prior to first drug administration or is concurrently enrolled in any research judged not to be scientifically or medically compatible with the study
- use of any prescription medication within 14 days prior to first study drug administration
- use of any OTC medications within 14 days prior to first study drug administration
- use of any prescription drugs, including MAO inhibitors, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, triptans, tricyclic antidepressants, fentanyl, lithium, buspirone, St. Johns Wort and all medications which are cytochrome P450 (CYP450) 2D6 inhibitors in the 30 days or 5 half-lives (whichever was longer) prior to first study drug administration
- use of any alkalinizing agents within 30 days prior to first study drug administration
- individuals having undergone any major surgery within 6 months prior to start of study, unless deemed not clinically significant by PI
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Treatment A
crushed d-amphetamine IR tablets
|
manipulated ADAIR IR 3x10 mg capsules
crushed d-amphetamine sulfate IR 6 x 5 mg tablets
|
Experimental: Treatment B
manipulated ADAIR IR capsules
|
manipulated ADAIR IR 3x10 mg capsules
crushed d-amphetamine sulfate IR 6 x 5 mg tablets
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Treatment-emergent adverse event reporting
Time Frame: Day 1 to Day 9 (Treatment Phase)
|
Assess the safety and tolerability as measured by the incidence, frequency, and severity of treatment-emergent adverse events
|
Day 1 to Day 9 (Treatment Phase)
|
Abnormal Vital Signs
Time Frame: Day 1 to Day 9 (Treatment Phase)
|
Number and percent of subjects with abnormal vital sign values
|
Day 1 to Day 9 (Treatment Phase)
|
Abnormal ECG Values
Time Frame: Day 1 to Day 9 (Treatment Phase)
|
Number and percent of abnormal ECG values
|
Day 1 to Day 9 (Treatment Phase)
|
Abnormal clinical laboratory results
Time Frame: Day 1 to Day 9 (Treatment Phase)
|
Number and percent of abnormal clinical laboratory results
|
Day 1 to Day 9 (Treatment Phase)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum Plasma Concentration (Cmax)
Time Frame: Up to 24 hours post dose
|
Maximum plasma concentration
|
Up to 24 hours post dose
|
Time to Maximum Plasma Concentration (tmax)
Time Frame: Up to 24 hours post dose
|
Time to maximum plasma concentration
|
Up to 24 hours post dose
|
Area Under the Plasma Concentration AUC0-1h
Time Frame: Up to 24 hours post dose
|
Area under the plasma concentration vs time curve from time 0 to 1 hour (AUC 0-1h)
|
Up to 24 hours post dose
|
Area Under the Plasma Concentration AUC0-2h
Time Frame: Up to 24 hours post dose
|
Area under the plasma concentration vs time curve from time 0 to 2 hours (AUC0-2h)
|
Up to 24 hours post dose
|
Area Under the Plasma Concentration AUC0-4h
Time Frame: Up to 24 hours post dose
|
Area under the plasma concentration vs time curve from time 0 to 4 hours (AUC0-4h)
|
Up to 24 hours post dose
|
Area Under the Plasma Concentration AUCt
Time Frame: Up to 24 hours post dose
|
Area under the plasma concentration vs time curve from time 0 to the time of the last measurable concentration, or last sampling time t (AUCt)
|
Up to 24 hours post dose
|
Area Under the Plasma Concentration AUCinf
Time Frame: Up to 24 hours post dose
|
Area under the plasma concentration vs time curve extrapolated to infinity (AUCinf)
|
Up to 24 hours post dose
|
Abuse quotient (AQ)
Time Frame: Up to 24 hours post dose
|
Abuse quotient (AQ): Cmax/tmax
|
Up to 24 hours post dose
|
Terminal elimination rate constant λz
Time Frame: Up to 24 hours post dose
|
Terminal elimination rate constant (λz)
|
Up to 24 hours post dose
|
Terminal elimination half-life t½
Time Frame: Up to 24 hours post dose
|
Terminal elimination half-life (t½)
|
Up to 24 hours post dose
|
Bipolar Ease of Snorting visual analog scale (VAS)
Time Frame: Up to 24 hours post dose
|
Bipolar Ease of Snorting VAS minimum (peak) effect (Emin)
|
Up to 24 hours post dose
|
Bipolar Likeability of Snorting VAS
Time Frame: Up to 24 hours post dose
|
Bipolar Likeability of Snorting VAS -minimum (peak) effect (Emin), maximum (peak) effect (Emax), time-averaged area under the effect curve from time 0 to 24 hours postdose (TA_AUE)
|
Up to 24 hours post dose
|
Bipolar Comfort of Snorting VAS
Time Frame: Up to 24 hours post dose
|
Bipolar Comfort of Snorting VAS - minimum (peak) effect (Emin), maximum (peak) effect (Emax), time-averaged area under the effect curve from time 0 to 24 hours postdose (TA_AUE)
|
Up to 24 hours post dose
|
Subject-Rated Assessment of Intranasal Irritation (SRAII)
Time Frame: Up to 24 hours post dose
|
Subject-Rated Assessment of Intranasal Irritation (SRAII) - maximum (peak) effect (Emax)and TEmax: time to maximum effect)
|
Up to 24 hours post dose
|
Percent of dose insufflated
Time Frame: 0 min (dosing time)
|
Percent of dose insufflated
|
0 min (dosing time)
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Abuse Liability
Time Frame: Up to 24 hours post dose
|
Abuse liability parameters measured by Visual Analogue Scales (VAS)
|
Up to 24 hours post dose
|
Subjective Drug Value Assessment
Time Frame: Up to 24 hours post dose
|
Assessment of subjective drug value up to 24 hours post dose
|
Up to 24 hours post dose
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Timothy Whitaker, MD, Vallon Pharmaceuticals, Inc.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Mental Disorders
- Nervous System Diseases
- Sleep Disorders, Intrinsic
- Dyssomnias
- Sleep Wake Disorders
- Disorders of Excessive Somnolence
- Narcolepsy
- Physiological Effects of Drugs
- Adrenergic Agents
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Autonomic Agents
- Peripheral Nervous System Agents
- Neurotransmitter Uptake Inhibitors
- Membrane Transport Modulators
- Dopamine Agents
- Dopamine Uptake Inhibitors
- Central Nervous System Stimulants
- Sympathomimetics
- Adrenergic Uptake Inhibitors
- Amphetamine
- Dextroamphetamine
Other Study ID Numbers
- VAL-103
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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