Clinical Trial to Evaluate the Safety and Efficacy of NRCT-101SR in Adult Attention Deficit Hyperactivity Disorder
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 223
- 试验地点
- 8
- 主要终点
- Change From Baseline in Permanent Product Measure of Performance (PERMP) - Number of Math Problems Answered Correctly (PERMP-C)
研究概览
简要总结
The goal of this clinical trial is to evaluate the efficacy and safety of NRCT-101SR compared to placebo in adult patients with ADHD aged 18 years and older.
详细描述
This is a multi-center, randomized, double-blind, placebo-controlled, parallel-arm design, laboratory classroom (LC) trial to assess the efficacy and safety of NRCT-101SR compared to inactive placebo for the treatment of ADHD in adults aged 18 years and older.
After Screening, Orientation, and Baseline evaluations are complete, eligible subjects will be randomized into one of two groups (1:1) to receive NRCT-101SR or matching placebo orally twice daily, in the morning and evening, beginning the day after the Baseline visit for 6 weeks. Subjects will receive a fixed dose of 1,500 or 2,000 mg/day, based on lean body mass, split evenly between the morning and evening dosing.
Total subject participation in the study is up to approximately 13 weeks, including a screening period (up to 6 weeks), a 6-week treatment period, and an approximate 1-week follow-up period. Within 8 days prior to Baseline LC visit, subjects will complete an LC Orientation Visit. LC visits will be repeated at Week 3 and Week 6.
The primary outcome measures of the study include Permanent Product Measure of Performance (PERMP) Math Tests (number of correctly answered problems; PERMP-C) and ADHD Investigator Symptom Rating Scale (AISRS). At Baseline, Week 3 visit, and Week 6 visit, serial PERMP Math Tests at pre-dose and at 2, 4, 6, 8, 10, and 12 hours post-dose, and AISRS will be administered. LC visits will be repeated at Week 3 and Week 6. Secondary and exploratory assessments will also be conducted at the Baseline, Week 3, and Week 6 LC visits. A clinic visit will be conducted at Week 1. Pharmacokinetic (PK) sampling will be collected at the Week 3 LC visit. Safety assessments (concomitant medications, adverse events, and suicide risk) will be conducted at all clinic and remote visits/phone calls (Week 5, and follow-up); safety labs will be conducted at screening, Week 3, and Week 6.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Double-blind
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female, ≥ 18 years of age at screening
- •Has a primary diagnosis of ADHD according to the Diagnostic and Statistical Manual, Fifth Edition (DSM-5) classification, confirmed with Mini International Neuropsychiatric Interview (MINI) using DSM-5 probes
- •AISRS ≥ 26 at screening and baseline, and does not change by more than 25% from screening to baseline, except subjects who stop taking ADHD medication after screening may have an increase of more than 25%
- •Has a minimum score of 4 on the CGI-S at baseline
- •Must be fluent in English, and capable of reading, writing, and communicating effectively with others and willing to participate in laboratory classroom
- •Completion of at least 10 years of formal education
- •Hearing and Vision ability sufficient to complete cognitive testing, in investigator's opinion
- •Willing and able to give informed consent
- •Total Body weight (bw) must be ≥ 50 kg and ≤ 105 kg and lean body mass (LBM) must be ≤ 75 kg at screening
- •Naïve to stimulant or non-stimulant medications used for the treatment of ADHD or have discontinued stimulants at least 2 weeks and non-stimulants at least 3 weeks prior to randomization
排除标准
- •Subject is functioning below an age-appropriate level intellectually, as judged by the investigator.
- •Lifetime history of severe psychiatric symptoms of major depression requiring hospitalization, bipolar disorder, schizophrenia of schizoaffective disorder, hallucinations, or delusions. Severe comorbid disorders such as PTSD, severe obsessive-compulsive disorder, or other symptomatic presentation that, in the opinion of the examining physician, will contraindicate NRCT-101SR treatment or confound efficacy or safety assessments. Subjects with mild to moderate forms of social phobia or dysthymia, for instance, may be included.
- •History of seizures (other than infantile febrile seizures), any tic disorder (except transient tic disorder and subject has no episodes for at least 1 year), or a current diagnosis of Tourette's Disorder.
- •Recent history (within the past 1 year) of suspected substance abuse or dependence disorder (excluding stable nicotine use) in accordance with DSM-5 criteria. (Note: subject's average nicotine use should not be exceeded during each LC visit)
- •Current abnormal thyroid function as defined as abnormal screening thyroid stimulating hormone. Treatment for at least 3 months with a stable dose of thyroid medication is permitted.
- •Poor kidney function; corrected estimated glomerular filtration rate (eGFRcorr) < 40 mL/min/m2
- •History of significant gastrointestinal disorders, such as chronic diarrhea, irritable bowel syndrome, ulcerative colitis, Crohn's disease, etc.
- •Female subjects who are pregnant and/or lactating
- •A "yes" answer to "suicidal ideation" item 4 (active suicidal ideation with some intent to act, without specific plan) or item 5 (active suicidal ideation with specific plan and intent) on the Columbia-Suicide Severity Rating Scale (C-SSRS) assessment at screening (in the past 12 months).
- •Has history of severe drug allergy or hypersensitivity to the study medication or its excipients.
- •Hypermagnesemia; magnesium > 2.5 mg/dL
- •Reproduction:
- •a. Females of childbearing potential (FOCP) must be either sexually inactive abstinent) or, if sexually active, must agree to use one of the following acceptable birth control methods beginning 30 days prior to the first dose of study drug and throughout the study: i. Simultaneous use of male condom and intra-uterine contraceptive device placed at least 4 weeks prior to first study drug administration ii. Surgically sterile male partner iii. Simultaneous use of male condom and diaphragm with spermicide iv. Established hormonal contraceptive b. Males must: i. Use 2 methods of contraception in combination if his female partner is of childbearing potential; this combination of contraceptive methods must be used from the Baseline Visit to ≥ 1 month after the last dose of study drug, or ii. Have been surgically sterilized prior to the Screening Visit.
- •Is currently participating in another clinical trial or has participated in a clinical trial within 30 days prior to the Screening Visit.
- •Currently living in an institutional facility such as a nursing home
- •Severe physical disability not associated with cognitive function that limits ability to complete testing (e.g., severe tremor, debilitating arthritis, etc.)
- •Known history of symptomatic cardiac disease, advanced atherosclerosis, structural cardiac abnormality, cardiomyopathy, serious heart rhythm abnormalities, coronary heart disease, transient ischemic attack or stroke or other serious cardiac problems.
- •Known family history of sudden cardiac death or ventricular arrhythmia.
- •Serious or unstable clinically important systemic illness or disease that, in the judgment of the investigator, is likely to affect cognitive assessment, deteriorate, or affect the subject's safety or ability to complete the study, including hepatic (e.g., Child-Pugh grade C), renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, immunologic, infectious, or hematologic disorders
- •Has previously participated in a NRCT-101SR investigational study or a study that includes the active ingredient of NRCT-101SR
- •Investigators and their immediate family members are not permitted to participate in the study.
- •Consumes more than a weekly average of: 2 drinks / day or more than 3 drinks in any day for males; 1 drink / day or more than 2 drinks in any day for females
- •Changes in medications or doses of medication as follows:
- •All allowed concomitant medications, supplements, or other substances must be at stable doses for at least 30 days prior to screening and must be kept as stable as medically possible during the trial. For allowed concomitant medications, any dosing change within 30 days of Screening may be allowed if, in the opinion of the investigator, it will not affect or influence study results.
研究组 & 干预措施
NRCT-101SR
Two-tiered fixed dose of 1,500 or 2,000 mg/day. Two NRCT-101SR tablets (375 mg or 500 mg based on lean body mass) by mouth twice daily
干预措施: NRCT-101-SR (Drug)
Matching Placebo
Two-tiered fixed dose of 1,500 or 2,000 mg/day. Two NRCT-101SR placebo tablets (375 mg or 500 mg based on lean body mass) by mouth twice daily
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in Permanent Product Measure of Performance (PERMP) - Number of Math Problems Answered Correctly (PERMP-C)
时间窗: Baseline and Week 6
PERMP is a skill adjusted math test. PERMP-C is the number of math problems answered correctly in a 10-minute session and typically ranges from 0-400 with higher scores indicating better performance. The mean of the post-dose timepoint scores will be used for evaluation.
Change From Baseline in ADHD Investigator Symptom Rating Scale (AISRS)
时间窗: Baseline and Week 6
AISRS consists of 18 items scored on a 4-point scale ranging from 0 (no symptoms) to 3 (severe symptoms) with a total score ranging from 0 to 54. Lower scores indicate less severe symptoms.
次要结局
- Responder Rate(Baseline and Week 6)
- Change From Baseline Behavior Rating Inventory of Executive Function - Adult Version (BRIEF-A)(Baseline and Week 6)
- Change From Baseline in Hospital Anxiety and Depression Scale (HADS)(Baseline and Week 6)
- Change From Baseline in Adult ADHD Quality of Life Scale (AAQoL)(Baseline and Week 6)
- Change From Baseline in the Clinical Global Impression - Severity (CGI-S)(Baseline and Week 6)
- Change From Baseline in the ADHD Investigator Symptom Rating Scale - Expanded Version (AISRS-EV)(Baseline and Week 6)