Amphetamine Extended-Release Tablets in the Treatment of Adults With ADHD

• ClinicalTrials.gov Identifier: NCT03834766
• Recruitment Status: Completed
• First Posted: February 8, 2019
• Last Update Posted: December 9, 2019
• Sponsor: Tris Pharma, Inc.
• Collaborator: Premier Research Group plc
• Information provided by (Responsible Party): Tris Pharma, Inc.

Study Description

Brief Summary:

To evaluate the efficacy of AMPH ER TAB compared to placebo in adult patients with ADHD aged 18 to 60 years.

Condition or disease	Intervention/treatment	Phase
ADHD	Drug: AMPH ER Tab 5, 10, 15 and 20 mg; Drug: AMPH ER Tab Matching Placebo 5, 10, 15 and 20 mg	Phase 3

Detailed Description:

This is a randomized, double-blind (DB), placebo-controlled, parallel, study to assess the efficacy and safety of AMPH ER TAB compared to placebo for the treatment of ADHD in adults aged 18 to 60 years.

After Screening and Baseline evaluations are complete, eligible subjects will be randomized in the study to take DB AMPH ER TAB or matching placebo orally once daily in the morning beginning the day after the Baseline visit for 5 weeks. Dose will be titrated on a weekly basis to reach 20 mg per day.Subjects who cannot tolerate the study drug will be discontinued from the study.

A Math Test placement test will be done at Screening or at Baseline. At Visit 5, efficacy assessments will include the administration of serial Math Tests at pre-dose and at 0.5, 1, 2, 4, 8, 10, 12, 13, and 14 hours post-dose.

Adult Investigator Symptom Rating Scale (AISRS) and Clinical Global Impression Scale Severity (CGI-S) will be conducted at Baseline and Visits 1 to 5. Digit Symbol Substitution Test (DSST) will be administered at Baseline and Visit 5.

Safety assessments will include treatment-emergent adverse events, physical examination, vital signs, body weight, Columbia Suicide Severity Rating Scale (C-SSRS), and direct questioning to assess for sleep, appetite, mood and psychotic events.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 130 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: This is a randomized, double-blind (DB), placebo-controlled, parallel study
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: AMPH ER Tab 5, 10, 15 & 20 mg Vs. Matching Placebo
• Primary Purpose: Treatment
• Official Title: Amphetamine Extended-Release Tablets in the Treatment of Adults With ADHD
• Actual Study Start Date: February 6, 2019
• Actual Primary Completion Date: October 19, 2019
• Actual Study Completion Date: October 19, 2019

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: AMPH ER Tab; Amphetamine Extended Release Tablets 5, 10, 15 and 20 mg	Drug: AMPH ER Tab 5, 10, 15 and 20 mg; Amphetamine; Other Name: Amphetamine Extended Release Tablets
Placebo Comparator: Matching Placebo; Matching Placebo Tablets 5, 10, 15 and 20 mg	Drug: AMPH ER Tab Matching Placebo 5, 10, 15 and 20 mg; Placebo; Other Name: Amphetamine Extended Release Tablets Matching Placebo

Outcome Measures

Primary Outcome Measures :

1. Math Test score over all post-dose time points assessed during the administration of serial Math Tests at Visit 5 [ Time Frame: 6 monts ]
   The primary efficacy endpoint will be assessed using a linear Mixed Model Repeated Measures (MMRM) analysis using SAS® PROC MIXED. The model will include treatment, time and treatment by time as fixed effects and subject as a random effect. Pre-dose Math Test score will be included as a covariate. The difference between AMPH ER TAB and placebo will be assessed at the alpha = 0.05 level of significance.

Secondary Outcome Measures :

1. Onset of clinical effect [ Time Frame: 6 months ]
   Defined as the first time point post-dose when treatment effect of AMPH ER TAB versus placebo, evaluated using Math Test scores (attempted + correct) is significant.
2. Duration of clinical effect [ Time Frame: 6 months ]
   Defined as the time between last time point to the first time point post-dose with significant treatment effect of AMPH ER TAB versus placebo evaluated using Math Test scores (attempted + correct).

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria

1. Male or female aged 18 to 60 years, inclusive at the time of Screening.
2. Diagnosed with ADHD using the DSM-5 criteria based on the Adults ADHD Clinical Diagnostic Scale (ACDS).
3. IQ within normal range based upon clinical opinion of the Investigator.
4. Baseline AISRS total score greater than or equal to 26.
5. Baseline score of 4 or higher in CGI-S.

6. Females who participate in this study will be of childbearing or non-childbearing potential:

   • Childbearing potential: Physically capable of becoming pregnant

   • Non-childbearing potential:

     • Permanently sterile (i.e., both ovaries removed, uterus removed, or bilateral tubal ligation for at least 6 weeks or documented successful hysteroscopic sterilization); and/or
     • Post-menopausal (no menstrual period for at least 12 consecutive months without any other medical cause).
7. Females of childbearing potential must be non-lactating and must have a negative serum pregnancy test at Screening.
8. Willing to use acceptable, effective methods of contraception.
9. Be able to attend the clinic regularly and reliably.
10. Be able to understand, read, write, and speak English fluently to complete the study related materials.
11. Be informed of the nature of the study and give written consent prior to any study procedure.

Exclusion Criteria:

1. Current or lifetime history of bipolar disorder or any psychotic disorder as established by Mini International Neuropsychiatric Interview (M.I.N.I.) 7.0.2.
2. Current history of major depression, generalized anxiety disorder, obsessive-compulsive disorder, panic disorder, or post-traumatic stress disorder as established by the M.I.N.I. 7.0.2.
3. Known history of chronic medical illnesses including untreated thyroid disease, peripheral vasculopathy, known structural cardiac disorders, serious cardiac conditions, serious arrhythmias, cardiomyopathy, and known family history of sudden death.
4. History of uncontrolled hypertension or a resting systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg. Subjects with well-controlled hypertension on a stable dose for at least 3 months of anti-hypertensives will be allowed to participate.

5. Have clinically significant findings in vital signs measurements at Screening including:

   • Systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg
   • Heart rate >100 bpm

6. Known history or presence of significant renal or hepatic disease, as indicated by clinical laboratory assessment:

   • Liver function test results ≥2 times the upper normal limit
   • Abnormal blood urea nitrogen, or creatinine levels
7. Clinically significant abnormal electrocardiogram or cardiac findings on physical examination (including the presence of a pathologic murmur).

8. Use of the following medications within 14 days of Baseline Visit:

   • Atomoxetine
   • Monoamine oxidase inhibitors (e.g., selegiline, isocarboxazid, phenelzine, tranylcypromine)
   • Tricyclic antidepressants (e.g., desipramine, protriptyline).

9. Use of the following medications within 3 days of Baseline Visit:

   • Gastrointestinal acidifying agents (e.g., guanethidine, reserpine, glutamic acid hydrochloride [HCl], ascorbic acid)
   • Urinary acidifying agents (e.g., ammonium chloride, sodium acid phosphate, methenamine salts).
10. Use of fluoxetine within 30 days of Baseline Visit.
11. Use of stimulant medications within 1 week of Baseline Visit.
12. Planned use of prohibited drugs or agents from the Screening visit through the end of the study.
13. Participation in a clinical study in which an investigational drug was administered within 30 days prior to Screening.
14. Abnormal clinically significant laboratory test values at Screening that, in the opinion of the Medical Monitor or Sponsor, would preclude study participation.
15. Known history of allergy/hypersensitivity to amphetamine or any of the components of AMPH ER TAB.
16. Known history of lack of clinical response to amphetamine based upon Investigator judgment.
17. Positive test result for HIV, Hepatitis B surface antigen, or Hepatitis C antibody.
18. Any uncontrolled medical condition that, in the opinion of Medical Monitor or Sponsor, would preclude study participation.
19. History or presence of alcohol dependence or substance abuse disorder according to DSM-5 or within the last 12 months.
20. Subject's inability or unwillingness to follow directions from the study research staff.
21. Answer of "yes" to questions 4 or 5 of the C-SSRS within the last 2 years.

Contacts and Locations

Locations

United States, Florida

Meridien Research

Bradenton, Florida, United States, 344201

Meridien Research, Inc.

Maitland, Florida, United States, 32751

United States, Nevada

Center for Psychiatry and Behavioral Medicine

Las Vegas, Nevada, United States, 89128

Sponsors and Collaborators

Tris Pharma, Inc.

Premier Research Group plc

Investigators

• Principal Investigator: Andrew J. Cutler, MD; Meridien Research Inc.

More Information

• Responsible Party: Tris Pharma, Inc.
• ClinicalTrials.gov Identifier: NCT03834766
• Other Study ID Numbers: TRI108-ADD-400
• First Posted: February 8, 2019
• Last Update Posted: December 9, 2019
• Last Verified: December 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Additional relevant MeSH terms:

Amphetamine; Central Nervous System Stimulants; Physiological Effects of Drugs; Sympathomimetics; Autonomic Agents; Peripheral Nervous System Agents; Dopamine Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Adrenergic Agents; Adrenergic Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Uptake Inhibitors