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Pilot Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Abuse Liability of an Abuse-Deterrent Immediate-Release Formulation (ADAIR)

Primary Purpose

ADHD, Narcolepsy

Status
Completed
Phase
Phase 1
Locations
Canada
Study Type
Interventional
Intervention
ADAIR 10mg IR capsules
Crushed d-amphetamine sulfate IR tablets
Sponsored by
Vallon Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for ADHD

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • BioPharma Services Inc.

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Treatment A

Treatment B

Arm Description

crushed d-amphetamine IR tablets

manipulated ADAIR IR capsules

Outcomes

Primary Outcome Measures

Treatment-emergent adverse event reporting
Assess the safety and tolerability as measured by the incidence, frequency, and severity of treatment-emergent adverse events
Abnormal Vital Signs
Number and percent of subjects with abnormal vital sign values
Abnormal ECG Values
Number and percent of abnormal ECG values
Abnormal clinical laboratory results
Number and percent of abnormal clinical laboratory results

Secondary Outcome Measures

Maximum Plasma Concentration (Cmax)
Maximum plasma concentration
Time to Maximum Plasma Concentration (tmax)
Time to maximum plasma concentration
Area Under the Plasma Concentration AUC0-1h
Area under the plasma concentration vs time curve from time 0 to 1 hour (AUC 0-1h)
Area Under the Plasma Concentration AUC0-2h
Area under the plasma concentration vs time curve from time 0 to 2 hours (AUC0-2h)
Area Under the Plasma Concentration AUC0-4h
Area under the plasma concentration vs time curve from time 0 to 4 hours (AUC0-4h)
Area Under the Plasma Concentration AUCt
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)
Area Under the Plasma Concentration AUCinf
Area under the plasma concentration vs time curve extrapolated to infinity (AUCinf)
Abuse quotient (AQ)
Abuse quotient (AQ): Cmax/tmax
Terminal elimination rate constant λz
Terminal elimination rate constant (λz)
Terminal elimination half-life t½
Terminal elimination half-life (t½)
Bipolar Ease of Snorting visual analog scale (VAS)
Bipolar Ease of Snorting VAS minimum (peak) effect (Emin)
Bipolar Likeability of Snorting VAS
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)
Bipolar Comfort of Snorting VAS
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)
Subject-Rated Assessment of Intranasal Irritation (SRAII)
Subject-Rated Assessment of Intranasal Irritation (SRAII) - maximum (peak) effect (Emax)and TEmax: time to maximum effect)
Percent of dose insufflated
Percent of dose insufflated

Full Information

First Posted
January 10, 2020
Last Updated
January 14, 2020
Sponsor
Vallon Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04232644
Brief Title
Pilot Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Abuse Liability of an Abuse-Deterrent Immediate-Release Formulation (ADAIR)
Official Title
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 Type
Interventional

2. Study Status

Record Verification Date
January 2020
Overall Recruitment Status
Completed
Study Start Date
May 27, 2019 (Actual)
Primary Completion Date
July 17, 2019 (Actual)
Study Completion Date
July 17, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Vallon Pharmaceuticals, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
This is a pilot randomized, double-blind, active-controlled, 2-treatment, crossover study to evaluate the PK, user experience and abuse liability of manipulated ADAIR compared to a manipulated commercially-available d-amphetamine sulfate IR formulation administered intranasally in non-dependent recreational stimulant users. The study is comprised of 4 phases: Screening, Qualification, Treatment, and Follow-up/Early Termination.
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
ADHD, Narcolepsy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
16 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment A
Arm Type
Active Comparator
Arm Description
crushed d-amphetamine IR tablets
Arm Title
Treatment B
Arm Type
Experimental
Arm Description
manipulated ADAIR IR capsules
Intervention Type
Drug
Intervention Name(s)
ADAIR 10mg IR capsules
Intervention Description
manipulated ADAIR IR 3x10 mg capsules
Intervention Type
Drug
Intervention Name(s)
Crushed d-amphetamine sulfate IR tablets
Intervention Description
crushed d-amphetamine sulfate IR 6 x 5 mg tablets
Primary Outcome Measure Information:
Title
Treatment-emergent adverse event reporting
Description
Assess the safety and tolerability as measured by the incidence, frequency, and severity of treatment-emergent adverse events
Time Frame
Day 1 to Day 9 (Treatment Phase)
Title
Abnormal Vital Signs
Description
Number and percent of subjects with abnormal vital sign values
Time Frame
Day 1 to Day 9 (Treatment Phase)
Title
Abnormal ECG Values
Description
Number and percent of abnormal ECG values
Time Frame
Day 1 to Day 9 (Treatment Phase)
Title
Abnormal clinical laboratory results
Description
Number and percent of abnormal clinical laboratory results
Time Frame
Day 1 to Day 9 (Treatment Phase)
Secondary Outcome Measure Information:
Title
Maximum Plasma Concentration (Cmax)
Description
Maximum plasma concentration
Time Frame
Up to 24 hours post dose
Title
Time to Maximum Plasma Concentration (tmax)
Description
Time to maximum plasma concentration
Time Frame
Up to 24 hours post dose
Title
Area Under the Plasma Concentration AUC0-1h
Description
Area under the plasma concentration vs time curve from time 0 to 1 hour (AUC 0-1h)
Time Frame
Up to 24 hours post dose
Title
Area Under the Plasma Concentration AUC0-2h
Description
Area under the plasma concentration vs time curve from time 0 to 2 hours (AUC0-2h)
Time Frame
Up to 24 hours post dose
Title
Area Under the Plasma Concentration AUC0-4h
Description
Area under the plasma concentration vs time curve from time 0 to 4 hours (AUC0-4h)
Time Frame
Up to 24 hours post dose
Title
Area Under the Plasma Concentration AUCt
Description
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)
Time Frame
Up to 24 hours post dose
Title
Area Under the Plasma Concentration AUCinf
Description
Area under the plasma concentration vs time curve extrapolated to infinity (AUCinf)
Time Frame
Up to 24 hours post dose
Title
Abuse quotient (AQ)
Description
Abuse quotient (AQ): Cmax/tmax
Time Frame
Up to 24 hours post dose
Title
Terminal elimination rate constant λz
Description
Terminal elimination rate constant (λz)
Time Frame
Up to 24 hours post dose
Title
Terminal elimination half-life t½
Description
Terminal elimination half-life (t½)
Time Frame
Up to 24 hours post dose
Title
Bipolar Ease of Snorting visual analog scale (VAS)
Description
Bipolar Ease of Snorting VAS minimum (peak) effect (Emin)
Time Frame
Up to 24 hours post dose
Title
Bipolar Likeability of Snorting VAS
Description
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)
Time Frame
Up to 24 hours post dose
Title
Bipolar Comfort of Snorting VAS
Description
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)
Time Frame
Up to 24 hours post dose
Title
Subject-Rated Assessment of Intranasal Irritation (SRAII)
Description
Subject-Rated Assessment of Intranasal Irritation (SRAII) - maximum (peak) effect (Emax)and TEmax: time to maximum effect)
Time Frame
Up to 24 hours post dose
Title
Percent of dose insufflated
Description
Percent of dose insufflated
Time Frame
0 min (dosing time)
Other Pre-specified Outcome Measures:
Title
Abuse Liability
Description
Abuse liability parameters measured by Visual Analogue Scales (VAS)
Time Frame
Up to 24 hours post dose
Title
Subjective Drug Value Assessment
Description
Assessment of subjective drug value up to 24 hours post dose
Time Frame
Up to 24 hours post dose

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Timothy Whitaker, MD
Organizational Affiliation
Vallon Pharmaceuticals, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
BioPharma Services Inc.
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M9L 3A2
Country
Canada

12. IPD Sharing Statement

Learn more about this trial

Pilot Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Abuse Liability of an Abuse-Deterrent Immediate-Release Formulation (ADAIR)

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