A Study of PDC-1421 Treatment in Adult Patients With Attention-Deficit Hyperactivity Disorder (ADHD)

A Phase II Tolerability and Efficacy Study of PDC-1421 Treatment in Adult Patients With Attention-Deficit Hyperactivity Disorder (ADHD), Part I

The primary objective of this trial was to determine the effective doses and treatment period of PDC-1421 Capsule in subjects with ADHD.

The secondary objective was to evaluate the safety of PDC-1421 Capsule in subjects receiving PDC-1421 at various dose levels.

Study Overview

• Status: Completed
• Conditions: Attention-Deficit Hyperactivity Disorder (ADHD)
• Intervention / Treatment: Drug: PDC-1421 Capsule

Detailed Description

This study was a Part I of Phase II study designed to evaluate the safety and efficacy in adult patients with ADHD. The Screening phase is intended for diagnosing and assessing the patient for possible inclusion in the study and for providing an adequate washout period. The targeted population of this Part I study is six subjects who met the intent-to-treat per-protocol basis.

Part I study is an open-label study, single-center, and dose escalation evaluation in six patients.

1. Low dose: Six subjects will be initially evaluated for safety and efficacy assessments at low-dose (1 PDC-1421capsule TID) for 28 days. The subject will return for visit once a week during the treatment period.
2. Checkpoint #1: There will be an evaluation with all safety assessments data to decide whether subjects pass the checkpoint to enter high-dose treatment or continue to receive a low-dose treatment by the investigator.
3. High dose: The subjects who pass Checkpoint #1 will be initially evaluated for safety and efficacy assessments at high-dose (2 PDC-1421 capsules TID) for 28 days. Subjects will return for visit biweekly during the treatment period.
4. Checkpoint #2: There will be an evaluation with all safety assessments data to decide whether this study passes the checkpoint to enter Part II by the investigators.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • UCSF Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Aged 18-70 years
2. Female subjects of child-bearing potential must test negative to pregnancy and use appropriate birth control method from the beginning of study to the 15 days later after ending of study
3. Subjects must be able to understand and willing to sign informed consent
4. Able to discontinue the use of any psychotropic medications for the treatment of ADHD symptoms at screening
5. Meet strict operational criteria for adult ADHD according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5)
6. A total score of 20 or higher on the 18-item total ADHD symptoms score of Conners' Adult Attention-Deficit/Hyperactivity Disorder Rating Scale-Self Report: Short Version (CAARS-S:S) at screening
7. Have a moderate or severe symptom of ADHD with score of 4 or higher in Clinical Global Impression-ADHD-Severity (CGI-ADHD-S) at screening

Exclusion Criteria:

1. Have any clinically significant concurrent medical condition (endocrine, renal, respiratory, cardiovascular, hematological, immunological, cerebrovascular, neurological, anorexia, obesity or malignancy) that has become unstable and may interfere with the interpretation of safety and efficacy evaluations
2. Have any clinically significant abnormal laboratory, vital sign, physical examination, or electrocardiogram (ECG) findings at screening that, in the opinion of the investigator, may interfere with the interpretation of safety or efficacy evaluations
3. Have known serological evidence of human immunodeficiency virus (HIV) antibody
4. Are pregnant as confirmed by a positive pregnancy test at screening
5. Have QTc values >450 msec at screening using Fridericia's QTc formula
6. Have current of bipolar and psychotic disorders
7. Have a current major depression disorder, obsessive-compulsive disorder, post-traumatic stress disorder, generalized anxiety disorder, panic disorder and eating disorder (also if treated but not currently symptomatic)
8. Have any history of a significant suicide attempt, or possess a current risk of attempting suicide, in the investigator's opinion, based on clinical interview and responses provided on the Beck Scale for Suicidal Ideation (BSS)
9. Have a history of jailing or imprisonment in the past 6 months due to worsening of symptoms of ADHD

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Low dose + Low dose; 1 PDC-1421 Capsule, trice daily, p.o. after meal for 28 + 28 days	Drug: PDC-1421 Capsule; PDC-1421 Capsule is a botanical investigational new drug containing the extract of Radix Polygalae (Polygala tenuifolia Willd.) as active ingredient.
EXPERIMENTAL: Low dose + High dose; 1 PDC-1421 Capsule for 28 days + 2 PDC-1421 Capsules for 28 days, trice daily, p.o. after meals	Drug: PDC-1421 Capsule; PDC-1421 Capsule is a botanical investigational new drug containing the extract of Radix Polygalae (Polygala tenuifolia Willd.) as active ingredient.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Improvement ≥ 40% in ADHD-RS-IV From Baseline up to 8 Weeks Treatment	The primary endpoint is the change of ADHD Rating Scale-IV (ADHD-RS-IV) total score from baseline up to Week 8 of treatment in ITT population. The ADHD-RS-IV with Adult Prompts is an 18-item scale base on the DSM-IV-TR criteria for ADHD that provides a rating of the severity of symptoms. The adult prompts serve as a guide to explore more fully the extent and severity of ADHD symptoms and create a framework to ascertain impairment. The odd-numbered 9 items assess inattentive symptoms and the even-numbered 9 items assess hyperactive-impulsive symptoms. Scoring is based on a 4-point, yielding a possible total score of 0-54. Likert-type severity scale: 0 = Never or Rarely, 1 = Sometimes, 2 = Often, 3 = Very Often. Clinicians should score the highest score that is generated for the prompts for each item. The ADHD-RS-IV was assessed from Visit 1 to Visit 8 by the investigator.	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in ITT Population From Baseline up to 4 and 8 Weeks Treatment in the Conners' Adult Attention-Deficit/Hyperactivity Disorder Rating Scale-Self Report: Short Version (CAARS-S:S) 5 Subscales T-score.	Conners' Adult Attention-Deficit/Hyperactivity Disorder Rating Scale-Self Report: Short Version (CAARS-S:S) consists of 26 items rated from 0=not at all, never to 3=very much, very frequently. Four subscales each composed of 5 items (A: inattention/memory problems; B: hyperactivity/restlessness; C: impulsivity/emotional lability; and D: problems with self-concept) as well as a 12-item ADHD index can be computed. The raw scores were converted into standard T-scores by the SAS program which was designed according to the Profile form of CAARS QuikScore forms. The higher T-scores represent a better or worse outcome. A T-score is a standard score with a mean of 50 and a standard deviation of 10 in all samples and across all scales.	8 weeks
Number of Participants With a CGI Score of 2 or Lower	Clinical Global Impression-Severity (CGI-S) and Clinical Global Impression-Improvement (CGI-I) score of 2 or lower. The CGI-S is rated on a 7-point scale, with the severity of illness scale using a range of responses from 1 (normal) through to 7 (amongst the most severely ill patients). CGI-I scores range from 1 (very much improved) through to 7 (very much worse).	8 weeks
Change in ITT Population From Baseline up to 4 and 8 Weeks in the ADHD-RS-IV Inattention Subscale, Hyperactivity-impulsivity Subscale, and Total Scale Raw Score.	The ADHD-RS-IV with Adult Prompts is an 18-item scale base on the DSM-IV-TR criteria for ADHD that provides a rating of the severity of symptoms. The adult prompts serve as a guide to explore more fully the extent and severity of ADHD symptoms and create a framework to ascertain impairment. The odd-numbered 9 items assess inattentive symptoms and the even-numbered 9 items assess hyperactive-impulsive symptoms. Scoring is based on a 4-point, yielding a possible summed "total score" of 0-54, "inattentive subscore" of 0-27, and "hyperactive-impulsive subscore" of 0-27. The higher values represent a worse outcome for the total score and subscore. Likert-type severity scale: 0 = Never or Rarely, 1 = Sometimes, 2 = Often, 3 = Very Often. . The ADHD-RS-IV was assessed from Visit 1 to Visit 8 by the investigator.	8 Weeks

Collaborators and Investigators

• Sponsor: BioLite, Inc.
• Investigators: Study Director: Keith R McBurnett, PhD, University of California San Francisco, School of Medicine

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 1, 2019
• Primary Completion (ACTUAL): July 15, 2020
• Study Completion (ACTUAL): July 15, 2020

Study Registration Dates

• First Submitted: March 1, 2016
• First Submitted That Met QC Criteria: March 3, 2016
• First Posted (ESTIMATE): March 4, 2016

Study Record Updates

• Last Update Posted (ACTUAL): December 1, 2021
• Last Update Submitted That Met QC Criteria: November 5, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: ADHD
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Dyskinesias; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Attention Deficit Disorder with Hyperactivity; Hyperkinesis
• Other Study ID Numbers: Phase II BLI-1008-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No