Attention-Deficit Hyperactivity Disorder (ADHD)
Conditions
Keywords
ADHD
Brief summary
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.
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.
Interventions
DRUGPDC-1421 Capsule
PDC-1421 Capsule is a botanical investigational new drug containing the extract of Radix Polygalae (Polygala tenuifolia Willd.) as active ingredient.
Sponsors
BioLite, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Improvement ≥ 40% in ADHD-RS-IV From Baseline up to 8 Weeks Treatment | 8 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 8 weeks | 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. |
| Number of Participants With a CGI Score of 2 or Lower | 8 weeks | 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). |
| 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. | 8 Weeks | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Low Dose + High Dose 1 PDC-1421 Capsule for 28 days + 2 PDC-1421 Capsules for 28 days, trice daily, p.o. after meals
PDC-1421 Capsule: PDC-1421 Capsule is a botanical investigational new drug containing the extract of Radix Polygalae (Polygala tenuifolia Willd.) as active ingredient. | 6 |
| Total | 6 |
Baseline characteristics
| Characteristic | Low Dose + High Dose | — |
|---|---|---|
| ADHD Rating Scale | 41.8 units on a scale STANDARD_DEVIATION 6.6 | — |
| Age, Continuous | 38.0 years | — |
| CAARS-S:S ADHD Index (T-score) | 73.5 T-scale STANDARD_DEVIATION 8.3 | — |
| CGI-severity | 5.3 score on a scale STANDARD_DEVIATION 0.5 | — |
| Height | 178.80 cm | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Sex: Female, Male Female | 2 Participants | — |
| Sex: Female, Male Male | 4 Participants | — |
| Weight | 170.0 lb | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 6 |
| other Total, other adverse events | 4 / 6 |
| serious Total, serious adverse events | 0 / 6 |
Outcome results
Primary
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.
Time frame: 8 weeks
Population: ITT population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Low Dose + High Dose (at Week 8) | Number of Participants With Improvement ≥ 40% in ADHD-RS-IV From Baseline up to 8 Weeks Treatment | 5 Participants |
Secondary
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.
Time frame: 8 Weeks
Population: ITT population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose + High Dose (at Week 8) | 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. | Total scale | -17.7 score on a scale | Standard Deviation 13.2 |
| Low Dose + High Dose (at Week 8) | 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. | Inattention subscale | -10.5 score on a scale | Standard Deviation 8.2 |
| Low Dose + High Dose (at Week 8) | 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. | Hyperactivity-impulsivity subscale | -7.2 score on a scale | Standard Deviation 5.3 |
| Low Dose + High Dose (Week 0-8) | 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. | Hyperactivity-impulsivity subscale | -10.5 score on a scale | Standard Deviation 4.1 |
| Low Dose + High Dose (Week 0-8) | 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. | Inattention subscale | -12.2 score on a scale | Standard Deviation 7.9 |
| Low Dose + High Dose (Week 0-8) | 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. | Total scale | -25.7 score on a scale | Standard Deviation 11 |
Secondary
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.
Time frame: 8 weeks
Population: ITT population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose + High Dose (at Week 8) | 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. | Hyperactivity subscale | -6.2 T-score | Standard Deviation 7.1 |
| Low Dose + High Dose (at Week 8) | 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. | Self-concept subscale | -5.7 T-score | Standard Deviation 7 |
| Low Dose + High Dose (at Week 8) | 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. | Impulsivity subscale | -10.8 T-score | Standard Deviation 7.1 |
| Low Dose + High Dose (at Week 8) | 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. | ADHD index subscale | -8.2 T-score | Standard Deviation 7.4 |
| Low Dose + High Dose (at Week 8) | 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. | Inattention/memory subscale | -10.0 T-score | Standard Deviation 10.2 |
| Low Dose + High Dose (Week 0-8) | 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. | ADHD index subscale | -10.8 T-score | Standard Deviation 6.2 |
| Low Dose + High Dose (Week 0-8) | 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. | Inattention/memory subscale | -10.5 T-score | Standard Deviation 11 |
| Low Dose + High Dose (Week 0-8) | 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. | Hyperactivity subscale | -5.2 T-score | Standard Deviation 5.9 |
| Low Dose + High Dose (Week 0-8) | 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. | Impulsivity subscale | -15.2 T-score | Standard Deviation 7.9 |
| Low Dose + High Dose (Week 0-8) | 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. | Self-concept subscale | -4.7 T-score | Standard Deviation 6.2 |
Secondary
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).
Time frame: 8 weeks
Population: ITT population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Low Dose + High Dose (at Week 8) | Number of Participants With a CGI Score of 2 or Lower | CGI-S | 0 Participants |
| Low Dose + High Dose (at Week 8) | Number of Participants With a CGI Score of 2 or Lower | CGI-I | 1 Participants |
| Low Dose + High Dose (Week 0-8) | Number of Participants With a CGI Score of 2 or Lower | CGI-S | 2 Participants |
| Low Dose + High Dose (Week 0-8) | Number of Participants With a CGI Score of 2 or Lower | CGI-I | 6 Participants |