An Exploratory Single Blind Study of Ergoloid Mesylates, 5-Hydroxytryptophan, and the Combination in Adult Males With Fragile X Syndrome
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Safety and Tolerability - Number of Treatment-Emergent Adverse Events
研究概览
简要总结
A preliminary assessment of the safety, tolerability and efficacy of Ergoloid mesylates (EM) and 5-hydroxytryptophan (5-HTP) and the combination (EM + 5-HTP) compared to placebo in males aged 18-45 years old with Fragile X Syndrome.
详细描述
This single-center, Phase 2, single-blind, 4-period sequential study will obtain a preliminary assessment of the effects of Ergoloid mesylates (EM) 1 mg TID and 5-hydroxytryptophan (5-HTP) 100 mg TID and the combination compared to a placebo period in males aged 18-45 years old with Fragile X Syndrome. The study will consist of a Screening period of up to 28 days prior to initial study drug administration, followed by four 4 week single-blind treatment periods (up to 21 weeks total). The screening and baseline visits may occur at the same time, provided the results of safety labs can be obtained. A final follow-up visit or phone contact for safety is planned one week after the conclusion of Period 4. Safety and tolerability assessments will include adverse event monitoring, vital signs, blood chemistry and hematology, and urinalysis. Brief cognitive and behavioral assessments will be performed during each clinic visit.
Eligible participants will progress through each of 4 periods (arms) on study. The periods are not listed sequentially here in order to preserve the single blind for participants. Throughout all 4 periods, participants will take two identical capsules three times a day. If only taking one over-encapsulated drug, they will take one over-encapsulated placebo pill with the drug at each dose, and when in period 4 they will take two over-encapsulated placebo pills at each dose.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Male aged 18 to 45 years, inclusive.
- •Participant has Fragile X Syndrome with a molecular genetic confirmation of the full Fragile X Mental Retardation (FMR1) mutation (≥200 CGG repeats).
- •Current treatment with no more than 3 prescribed psychotropic medications. Anti-epileptic medications are permitted and are not counted as psychotropic medications if they are used for treatment of seizures. Anti-epileptics for other indications, such as the treatment of mood disorders, count towards the limit of permitted medications.
- •Permitted concomitant psychotropic medications must be at a stable dose and dosing regimen for at least 2 weeks prior to Screening and must remain stable during the period between Screening and the commencement of study medication.
- •Anti-epileptic medications must be at a stable dose and dosing regimen for 12 weeks prior to Screening and must remain stable during the period between Screening and the commencement of study medication.
- •Participants with a history of seizure disorder who are currently receiving treatment with anti-epileptics must have been seizure-free for 3 months preceding screening, or must be seizure-free for 3 years if not currently receiving anti-epileptics.
- •Behavioral and therapy treatments/interventions must be stable for 4 weeks prior to Screening and must remain stable during the period between Screening and the commencement of study medication, and throughout the study. Minor changes in hours or times of therapy that are not considered clinically significant will not be exclusionary. Changes in therapies provided through a school program, due to school vacations, are allowed.
- •Participant must be willing to practice barrier methods of contraception while on study, if sexually active. Abstinence is also considered a reasonable form of birth control in this study population.
- •Participant has a parent, legal authorized guardian or consistent caregiver.
- •Participant and caregiver are able to attend the clinic regularly and reliably.
- •Participant is able to swallow capsules.
- •For participants who are not their own legal guardian, participant's parent/legal authorized guardian is able to understand and sign an informed consent form to participate in the study.
- •If participant is his own legal guardian, he can understand and sign informed consent to participate in the study.
- •If participant is not their own legal guardian, the participant provides assent for participation in the study, if the participant has the cognitive ability to provide assent.
排除标准
- •History of, or current cardiovascular, renal, hepatic, respiratory, gastrointestinal, psychiatric, neurologic, cerebrovascular, or other systemic disease that would place the participant at risk or potentially interfere with the interpretation of the safety, tolerability, or efficacy of the study medication.
- •Common diseases such as mild hypertension, well-controlled type 2 diabetes mellitus (hemoglobin A1C [Hgb A1C] <6.5%), etc. are allowed per the investigator's judgment as long as they are stable and controlled by medical therapy that is constant for at least 4 weeks before randomization.
- •Clinically significant abnormalities, in the investigator's judgment, in safety laboratory tests, vital signs, as measured during Screening.
- •History of substance abuse within the past year, according to investigator assessment.
- •Use of CYP3A4 inhibitors, beta-blockers, MAO inhibitors or triptans at any time during participation in the study.
- •Significant hearing or visual impairment that may affect the participant's ability to complete the test procedures.
- •Concurrent major psychiatric condition (e.g., Major Depressive Disorder, Schizophrenia or Bipolar Disorder) as diagnosed by the investigator. Participants with additional diagnosis of Autism Spectrum Disorder or Anxiety Disorder will be allowed as these are characteristics of FXS.
- •Participant has active diseases that would interfere with participation, such as acquired immunodeficiency disorder, hepatitis C, hepatitis B, or tuberculosis.
- •Participant is planning to commence psychotherapy or cognitive behavior therapy (CBT) during the period of the study or had begun psychotherapy or CBT within 4 weeks prior to Screening.
- •Participant has participated in another clinical trial within the 30 days preceding Screening.
研究组 & 干预措施
Ergoloid mesylates (EM)
During treatment period 1, subjects will receive EM 1 mg (Medisca) and matching placebo for 5-HTP 100mg (ascorbic acid powder). One of each capsule (both size 00) will be taken three times per day for four weeks.
干预措施: Ergoloid Mesylates (Drug)
Ergoloid mesylates (EM)
During treatment period 1, subjects will receive EM 1 mg (Medisca) and matching placebo for 5-HTP 100mg (ascorbic acid powder). One of each capsule (both size 00) will be taken three times per day for four weeks.
干预措施: Matching placebo for 5-Hydroxytryptophan (Drug)
Ergoloid mesylates (EM) and 5-hydroxytryptophan (5-HTP)
During treatment period 2, subjects will receive EM 1 mg (Medisca) and 5-HTP 100 mg (5-HTP, Basic Vitamins). One of each capsule (both size 00) will be taken three times per day for four weeks.
干预措施: 5-Hydroxytryptophan (Drug)
Ergoloid mesylates (EM) and 5-hydroxytryptophan (5-HTP)
During treatment period 2, subjects will receive EM 1 mg (Medisca) and 5-HTP 100 mg (5-HTP, Basic Vitamins). One of each capsule (both size 00) will be taken three times per day for four weeks.
干预措施: Ergoloid Mesylates (Drug)
5-hydroxytryptophan (5-HTP)
During treatment period 3, subjects will receive 5-HTP 100 mg (5-HTP, Basic Vitamins) and matching placebo for EM 1 mg (ascorbic acid powder). One of each capsule (both size 00) will be taken three times per day for four weeks.
干预措施: 5-Hydroxytryptophan (Drug)
5-hydroxytryptophan (5-HTP)
During treatment period 3, subjects will receive 5-HTP 100 mg (5-HTP, Basic Vitamins) and matching placebo for EM 1 mg (ascorbic acid powder). One of each capsule (both size 00) will be taken three times per day for four weeks.
干预措施: Matching placebo for Ergoloid mesylates (Drug)
Placebo
During treatment period 4, subjects will receive matching placebo for EM 1mg (ascorbic acid powder) and matching placebo for 5-Hydroxytryptophan 100mg (ascorbic acid powder). One of each capsule (both size 00) will be taken three times per day for four weeks.
干预措施: Matching placebo for Ergoloid mesylates (Drug)
Placebo
During treatment period 4, subjects will receive matching placebo for EM 1mg (ascorbic acid powder) and matching placebo for 5-Hydroxytryptophan 100mg (ascorbic acid powder). One of each capsule (both size 00) will be taken three times per day for four weeks.
干预措施: Matching placebo for 5-Hydroxytryptophan (Drug)
结局指标
主要结局
Safety and Tolerability - Number of Treatment-Emergent Adverse Events
时间窗: Baseline through Week 17
Adverse Events (AEs), including clinically meaningful laboratory abnormalities and significant behavioral changes will be recorded from the time of the subject's first dose of study drug to the end of the study (Week 17) or longer if needed. Adverse events will be assessed at each visit as well as during each phone call and will be tabulated for each treatment period.
Safety and Tolerability - Severity of Treatment Emergent Adverse Events
时间窗: Baseline through Week 17
Adverse Events (AEs), including clinically meaningful laboratory abnormalities and significant behavioral changes will be tabulated for each treatment period. The Investigator is responsible for assessing the severity (intensity) of each adverse event as mild, moderate, or severe according to the following definitions: Mild - An event that is easily tolerated and generally not interfering with normal daily activities. Moderate - An event that is sufficiently discomforting to interfere with normal daily activities. Severe - An event that is incapacitating with inability to work or perform normal daily activities.
次要结局
- Change From Baseline in KiTAP Executive Battery - Alertness Subscore (Reaction Time)(Baseline, Week 4 (EM Treatment), Week 8 (EM+5-HTP Treatment), Week 12 (5-HTP Treatment), Week 16 (Placebo Treatment))
- Change From Baseline in Total Number of Correct Responses on KiTAP Executive Battery Distractibility Subtest(Baseline, Week 4 (EM Treatment), Week 8 (EM+5-HTP Treatment), Week 12 (5-HTP Treatment), Week 16 (Placebo Treatment))
- Change From Baseline in Total Number of Errors on KiTAP Executive Battery Distractibility Subtest(Baseline, Week 4 (EM Treatment), Week 8 (EM+5-HTP Treatment), Week 12 (5-HTP Treatment), Week 16 (Placebo Treatment))
- Change From Baseline in Total Number of Correct Responses on KiTAP Executive Battery Flexibility Subtest(Baseline, Week 4 (EM Treatment), Week 8 (EM+5-HTP Treatment), Week 12 (5-HTP Treatment), Week 16 (Placebo Treatment))
- Change From Baseline in Total Number of Errors on KiTAP Executive Battery Flexibility Subtest(Baseline, Week 4 (EM Treatment), Week 8 (EM+5-HTP Treatment), Week 12 (5-HTP Treatment), Week 16 (Placebo Treatment))
- Change From Baseline in Total Number of Correct Responses on KiTAP Test of Attentional Performance Go-NoGo Subtest(Baseline, Week 4 (EM Treatment), Week 8 (EM+5-HTP Treatment), Week 12 (5-HTP Treatment), Week 16 (Placebo Treatment))
- Change From Baseline in Total Number of Errors on KiTAP Test of Attentional Performance Go-NoGo Subtest(Baseline, Week 4 (EM Treatment), Week 8 (EM+5-HTP Treatment), Week 12 (5-HTP Treatment), Week 16 (Placebo Treatment))
- Change From Baseline in Clinical Global Impression Severity Scale Overall Score(Baseline, Week 4 (EM Treatment), Week 8 (EM+5-HTP Treatment), Week 12 (5-HTP Treatment), Week 16 (Placebo Treatment))
- Change From Baseline in Aberrant Behavior Checklist (ABC) Subscores(Baseline, Week 4 (EM Treatment), Week 8 (EM+5-HTP Treatment), Week 12 (5-HTP Treatment), Week 16 (Placebo Treatment))
- Change From Baseline in Anxiety, Depression, and Mood Scale (ADAMS) Subscores(Baseline, Week 4 (EM Treatment), Week 8 (EM+5-HTP Treatment), Week 12 (5-HTP Treatment), Week 16 (Placebo Treatment))
- Change From Baseline on Vineland-3 Adaptive Behavior Scale - Subdomain Growth Scale Values(Baseline, Week 4 (EM Treatment), Week 8 (EM+5-HTP Treatment), Week 12 (5-HTP Treatment), Week 16 (Placebo Treatment))
- Change From Baseline in NIH Toolbox Cognitive Battery for Intellectual Disabilities (NIH-TCB) Total Cognition Score(Baseline, Week 4 (EM Treatment), Week 8 (EM+5-HTP Treatment), Week 12 (5-HTP Treatment), Week 16 (Placebo Treatment))
- Change From Baseline in Visual Analog Scale (VAS) Assessment Domain Scores(Baseline, Week 4 (EM Treatment), Week 8 (EM+5-HTP Treatment), Week 12 (5-HTP Treatment), Week 16 (Placebo Treatment))
- Event-Related Potentials (ERP) - Gamma Band Absolute Power at Resting State (Frontal)(Baseline, Week 4 (EM Treatment), Week 8 (EM+5-HTP Treatment), Week 12 (5-HTP Treatment), Week 16 (Placebo Treatment))
- Event-Related Potentials (ERP) Components in Response to Standard Tones(Baseline, Week 4 (EM Treatment), Week 8 (EM+5-HTP Treatment), Week 12 (5-HTP Treatment), Week 16 (Placebo Treatment))
- Event-Related Potentials - Frontal Alpha Asymmetry at Resting State(Baseline, Week 4 (EM Treatment), Week 8 (EM+5-HTP Treatment), Week 12 (5-HTP Treatment), Week 16 (Placebo Treatment))
研究者
Elizabeth Berry-Kravis
Professor, Department of Pediatrics, Neurological Sciences, Biochemistry
Rush University Medical Center