PDC-1421 Treatment in Adult Patients With ADHD

Study Overview
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Brief Summary
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Part II is a double-blind, randomized, parallel-group, placebo-controlled study. The primary objective of this trial is to determine the effective doses and treatment period of PDC-1421 Capsule in subjects with ADHD. The secondary objective is to evaluate the safety of PDC-1421 Capsule in subjects receiving PDC-1421 at various dose levels.

Detailed Description
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The screening phase is intended for diagnosing and assessing the patient for possible inclusion in the study and for providing an adequate washout period. At the first stage, a number of 69 subjects will be randomly assigned on a 1:1:1 basis to one of the three arms (1 PDC-1421 Capsule plus 1 placebo TID, 2 PDC-1421 Capsules TID, 2 placebo TID) for 8 weeks and evaluated the safety and efficacy every two weeks during the treatment period. An interim analysis will be conducted to evaluate the efficacy of PDC-1421 and to decide whether it is necessary to enter the second stage of the Part II study in which 30 subjects will be randomly assigned on a 1:1:1 basis to one of the three treatment arms and receive the same treatment. Simple descriptive statistics with a 95% confidence interval will be performed with data collected in this study wherever applicable. The safety and efficacy data will be analyzed using the non-parametric method wherever appropriate. The primary endpoint will be analyzed by chi-square test, while the secondary endpoints will be analyzed using the ANOVA or Kruskal-Wallis non-parametric ANOVA test for continuous endpoints and chi-square test for binary endpoints.

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

Conditions
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Attention-Deficit Hyperactivity Disorder (ADHD)

Intervention / Treatment
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* Drug: PDC-1421 Capsule
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18-70 years 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 Subjects must be able to understand and willing to sign informed consent Able to discontinue the use of any psychotropic medications for the treatment of ADHD symptoms at screening Meet strict operational criteria for adult ADHD according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) A total score of 28 or higher of ADHD Rating Scale-Investigator Rated (ADHD-RS-IV) at screening Have a moderate or severe symptom of ADHD with score of 4 or higher in Clinical Global Impression- Severity (CGI-S) at screening Exclusion Criteria: 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 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 Have known serological evidence of human immunodeficiency virus (HIV) antibody Are pregnant as confirmed by a positive pregnancy test at screening Have QTc values >450 msec at screening using Fridericia's QTc formula Have current of bipolar and psychotic disorders 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) NOTE: Comorbid diagnoses identified during screening and baseline are acceptable provided that ADHD is the primary diagnosis and the comorbid diagnoses will not confound study data or impair subject's ability to participate (per the Investigator's judgement and documented in source note). 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 Columbia-Suicide Severity Rating Scale (C-SSRS). Have a history of jailing or imprisonment in the past 6 months due to worsening of symptoms of ADHD

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants are assigned to one of three groups in parallel for the duration of the study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Two placebo capsules thrice daily for 56 days (8 weeks). | Drug: Placebo<br>* The placebo contained corn starch.<br>* Other names: Corn Starch;|
| Experimental: Low-dose<br>One placebo capsule and 1 PDC-1421 Capsule, thrice daily for 56 days (8 weeks). | Drug: PDC-1421 Capsule<br>* PDC-1421 Capsule is a botanical investigational new drug containing the extract of Radix Polygalae (Polygala tenuifolia Willd.) as the active ingredient.<br>* Other names: Extract of Radix Polygalae;Drug: Placebo<br>* The placebo contained corn starch.<br>* Other names: Corn Starch;|
| Experimental: High-dose<br>Two PDC-1421 Capsules thrice daily for 56 days (8 weeks). | Drug: PDC-1421 Capsule<br>* PDC-1421 Capsule is a botanical investigational new drug containing the extract of Radix Polygalae (Polygala tenuifolia Willd.) as the active ingredient.<br>* Other names: Extract of Radix Polygalae;|

What is the study measuring?
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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 ADHD-RS-IV with Adult Prompts is an 18-item scale based 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 7 by the investigator. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline up to 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 Quik Score 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 | 
| Change From Baseline up to 8 Weeks in the Sluggish Cognitive Tempo (K-SCT) Score. | The K-SCT rating scale queries 15 Sluggish Cognitive Tempo symptoms rated from 0 = Never or Rarely, 1 = Sometimes, 2 = Often, 3 = Very Often, grouped into latent factors of daydreaming, working memory problems, and subjective sleepiness/tiredness. The range for the Total Score is 0-45. The higher values represent a worse outcome for the total score and subscore. | 8 weeks | 
| Change From Baseline up to 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. | 8 weeks | 
| Number of Participants With Symptom Remission in ADHD-RS-IV From Baseline up to 8 Weeks Treatment | 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. | 8 weeks | 
| Number of Participants With a CGI Score of 2 or Lower From Baseline up to 8 Weeks Treatment | 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 |