Open-label Study to Evaluate Long-Term Safety and Efficacy of SPN-812 in Adults With ADHD

• ClinicalTrials.gov Identifier: NCT04143217
• Recruitment Status: Not yet recruiting
• First Posted: October 29, 2019
• Last Update Posted: November 12, 2019
• Sponsor: Supernus Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Supernus Pharmaceuticals, Inc.

Study Description

Brief Summary:

Open label, flexible dose, long-term multicenter study of safety and efficacy of SPN-812 in adult ADHD patients

Condition or disease	Intervention/treatment	Phase
Attention-Deficit/Hyperactivity Disorder	Drug: SPN-812	Phase 3

Detailed Description:

This is a multicenter, open-label extension study aimed to assess long-term safety and efficacy of SPN-812 when administered alone or in conjunction with an Food and Drug Administration-approved Attention Deficit Hyperactivity Disorder (ADHD) medication in the treatment of ADHD in adult subjects who have participated in a previous blinded study of SPN-812 (812P306). All adult subjects who completed the blinded study of SPN-812 will have the option to participate in this study in which all subjects receive SPN-812 at an optimized dose. Subjects will initiate SPN-812 dosing at 200 mg/day once daily (QD) for 1 week, then titrate to 400 mg/day at start of Week 2. It is recommended that subjects remain on 400 mg/day during Week 3. At or after Visit 3 (Week 4), per the Investigator's discretion and based on Investigator assessment of the subject's clinical response and tolerability, the dose of SPN-812 can be titrated up or tapered down in increments of 50 mg/day, 100 mg/day, 150 mg/day, or 200 mg/day per week to a target dose within the ranges between 200 and 600 mg/day. Additionally, after 3 months of dosing (after Visit 4), at the discretion of the Investigator and based on the subject's clinical response, the optimized dose of SPN-812 may be supplemented with an adjunctive FDA-approved stimulant treatment. The total study duration per subject from Visit 1 to the EOS (Visit 9) will be ~52 weeks or until SPN-812 becomes commercially available.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 400 participants
• Intervention Model: Single Group Assignment
• Intervention Model Description: Single Group Assignment
• Masking: None (Open Label)
• Masking Description: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label Extension Study to Evaluate the Long-Term Safety and Efficacy of SPN-812 in Adults With Attention-Deficit/Hyperactivity Disorder
• Estimated Study Start Date: December 2019
• Estimated Primary Completion Date: July 2021
• Estimated Study Completion Date: July 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Open-Label Treatment	Drug: SPN-812; SPN-812 200 to 600 mg

Outcome Measures

Primary Outcome Measures :

1. Incidence of adverse events [ Time Frame: 2 weeks - 4 weeks ]
   Change from baseline

Secondary Outcome Measures :

1. ADHD symptoms as measured by the Adult ADHD Investigator Symptom Rating Scale (AISRS) total score [ Time Frame: 2 weeks - 8 weeks ]
   Change from baseline in Adult ADHD Investigator Symptom Rating Scale (AISRS) total score
2. Global assessment of severity as measured by the Clinical Global Impression - Severity of Illness (CGI-S) scale for ADHD [ Time Frame: 52 weeks ]
   Change from baseline in CGI-S
3. Clinical response rate of severity of illness as measured by the categorical CGI-S Responder Rate (CGI-S score of 1 or 2) [ Time Frame: 2 weeks - 8 weeks ]
   Percentage of subjects with a CGI-S score of 1 or 2: score of 1=Normal; score of 2=Borderline ill
4. Global assessment of improvement as measured by the Clinical Global Impression - Improvement scale (CGI-I) for ADHD [ Time Frame: 2 weeks - 8 weeks ]
   CGI-I score by visit
5. Clinical response rate of improvement as measured by the categorical CGI-I Responder Rate (CGI-I score of 1 or 2) [ Time Frame: 2 weeks - 8 weeks ]
   Percentage of subjects with CGI-I score of 1 or 2; score of 1 = Very much improved; score of 2 = Much improved
6. Anxiety symptoms as measured by the Generalized Anxiety Disorder 7-Item scale (GAD-7) [ Time Frame: 2 weeks - 8 weeks ]
   Change from baseline in the GAD-7 total score by visit
7. Clinician-rated ADHD symptoms as measured by the AISRS subscales of Inattention and Hyperactivity/Impulsivity [ Time Frame: 2 weeks - 8 weeks ]
   Change from baseline in the AISRS Inattention subscale score and Hyperactivity/Impulsivity subscale scores by visit
8. Clinician response rate of ADHD symptom reduction as measured by the 50% responder rate in Adult ADHD Investigator Symptom Rating Scale (AISRS total score) [ Time Frame: 2 weeks - 8 weeks ]
   AISRS 50% responder rate (defined as the percentage of subjects with a ≥ 50% reduction in the CFB AISRS total score) by visit
9. Clinician response rate of ADHD symptom reduction as measured by the 30% responder rate in Adult ADHD Investigator Symptom Rating Scale (AISRS) total score [ Time Frame: 2 weeks - 8 weeks ]
   AISRS 30% responder rate (defined as the percentage of subjects with a ≥ 30% reduction in the CFB AISRS total score) by visit
10. Executive functioning as measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) [ Time Frame: 4 weeks - 8 weeks ]
    Change from Baseline in the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) T-score by visit
11. Aspects of executive function and problems of self-regulation as measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Summary Index Scales and subscales [ Time Frame: 2 weeks - 8 weeks ]
    Change from baseline in the BRIEF-A T-score by each Summary Index Scale and subscale by visit

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Is a male or female who completed Study 812P306 and opt/consent to participate in the study if approved by PI.
2. Continues to be medically healthy with clinically normal laboratory profiles, vital signs, and electrocardiograms (ECGs), in the opinion of the Investigator, as assessed at Visit 1.
3. Is able to read and understand the Informed Consent Form (ICF).
4. Has signed the ICF.
5. Is willing and able to attend study appointments within specified time windows.

6. Is a female of childbearing potential (FOCP) who is either sexually inactive (abstinent) or, if sexually active, agrees to use one of the following acceptable birth control methods beginning at least 30 days prior to the first dose of SM and throughout the study:

   1. Simultaneous use of male condom and intra-uterine contraceptive device placed at least 4 weeks prior to first SM administration
   2. Surgically sterile male partner
   3. Simultaneous use of male condom and diaphragm with spermicide
   4. Established hormonal contraceptive Females are considered not to be of childbearing potential if they are either post-menopausal (amenorrhea for at least 2 years and serum follicle stimulating hormone [FSH] level of >40 IU/L) or permanently sterilized (e.g., bilateral tubal ligation, hysterectomy, bilateral oophorectomy for 6 months minimum prior to their Visit 1).

7. Is a male who:

   1. Agrees to use 2 methods of contraception in combination if his female partner is of childbearing potential; this combination of contraceptive methods must be used from Visit 1 to ≥ 1 month after the last dose of SM, OR;
   2. Has been surgically sterilized prior to Visit 1.

Exclusion Criteria:

1. Is currently participating in another clinical trial other than Study 812P306.
2. Has any current psychiatric disorder per Diagnostic and Statistical Manual of Mental Disorders - 5th Edition (DSM-5) criteria other than ADHD with the following exceptions: ADHD is primary diagnoses with comorbidity/secondary diagnoses of major depression disorder (MDD), nicotine dependence, social anxiety disorder, generalized anxiety disorder, or phobias.
3. Current diagnosis of significant systemic disease and/or of a major psychiatric or neurological disorder, including history or family history of seizures or seizure-like disorders.
4. Current evidence of suicidality (suicidal thoughts or behaviors).
5. Female subjects who are pregnant, lactating and/or sexually active and not agreeing to use one of the acceptable birth control methods throughout the study.
6. Has a positive result on urine drug screen at Visit 1.
7. Use of prohibited concomitant medications including known CYP1A2 substrates (e.g., theophylline, melatonin) at the Visit 1 for the duration of the study.
8. Has a clinical laboratory value, vital sign value or ECG result at Visit 1 that is considered to be clinically significant in the opinion of the Investigator.

9. Has one or more clinical laboratory test values outside the reference range at Visit 1 that, in the opinion of the Investigator, are clinically significant, or any of the following:

   1. Serum creatinine > 1.5 times the upper limit of normal (ULN);
   2. Serum total bilirubin > 1.5 times ULN;
   3. Serum alanine aminotransferase or aspartate aminotransferase > 2 times ULN.

10. Has any of the following cardiology findings at Visit 1:

    1. Abnormal ECG that is, in the Investigator's opinion, clinically significant;
    2. PR interval > 220 ms;
    3. QRS interval > 130 ms;
    4. QTcF interval > 450 ms (for men) or > 470 ms (for women) (QT corrected using Fridericia's method);
    5. Second- or third-degree atrioventricular block;
    6. Any rhythm, other than sinus rhythm, that is interpreted by the Investigator to be clinically significant.
11. Any reason that, in the opinion of the Investigator, would prevent the subject from participating in the study.

Contacts and Locations

Contacts

Contact: Joseph T Hull, PhD; 240-403-5324; jhull@supernus.com

Contact: Lily Makannah; 240.403.5655; lmakannah@supernus.com

Sponsors and Collaborators

Supernus Pharmaceuticals, Inc.

Investigators

• Study Director: Stefan Schwabe, MD; Chief Medical Officer

More Information

• Responsible Party: Supernus Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT04143217
• Other Study ID Numbers: 812P311
• First Posted: October 29, 2019
• Last Update Posted: November 12, 2019
• Last Verified: October 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:

Hyperkinesis; Attention Deficit Disorder with Hyperactivity; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders; Dyskinesias; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms