A 10-week Efficacy Study of NOE-105 in Childhood Onset Fluency Disorder (Orpheus)

Study Overview
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Brief Summary
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This study is designed to evaluate the effectiveness of NOE-105 on speech fluency without the known antipsychotic-induced side effects of commonly used treatments for childhood onset fluency disorder (COFD).

Detailed Description
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NOE-105 is an investigational selective PDE10A inhibitor with a potential therapeutic effect for the treatment of COFD. In this study adult male patients may be randomized to a double-blind, placebo-controlled, parallel group treatment with NOE-105 or placebo once daily. The study is designed to find the maximum tolerated dose of NOE-105 and thereafter, to maintain the participants at this dose until they have completed a total of 10 weeks treatment period. Following up to 10 weeks of treatment, participants will visit the study site for a follow-up visit within 28 (± 7) days of the date of the last dose of study treatment.

Official Title
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A Double-blind, Placebo-controlled, Phase IIb, Multi-center, Ten-week Prospective Study to Evaluate the Efficacy and Safety of NOE-105 in Adult Male Patients With Childhood Onset Fluency Disorder (Orpheus)

Conditions
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Childhood-Onset Fluency Disorder

Intervention / Treatment
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* Drug: NOE-105
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must be 18 to 55 years of age inclusive, at the time of signing the informed consent. Patients who satisfy DSM-5 criteria for childhood onset fluency disorder and are suitable for pharmacotherapy. Have a history of stuttering for more than or equal to ≥ 2 years with onset consistent to developmental in nature before age 8 years. Patient reported global stuttering experience as moderate at screening and baseline. Patients must discontinue all medications used to treat stuttering for at least 14 days prior to receiving study treatment. With the exception of antipsychotic therapies (see exclusion criterion #11), other psychotropic drugs will be allowed provided they have been stable for at least 14 days prior to receiving study treatment and are expected to remain stable for the duration of the study. BMI within the range 19 to 35 kg/m2 (inclusive). Male Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Male patients must use a condom during the treatment period and until the end of relevant systemic exposure in the male participant, plus a further 90-day period. In addition, for a non-pregnant WOCBP partner. Capable of giving signed informed consent Able to read and write in English Exclusion Criteria: Stuttering is related to a known neurological cause eg, stroke, etc. Low IQ in the opinion of the investigator. Patients with uncontrolled seizure disorders. A history of severe traumatic brain injury or stroke. Patients who are, in the investigator's opinion, at imminent risk of suicide. Known to have tested positive for human immunodeficiency virus. Known DSM-5 diagnosis of substance abuse or dependence. Unstable medical illness or clinically significant abnormalities on screening tests/exams. Any unstable medical conditions or are currently ill (eg, congenital heart disease, arrhythmia or cancer), which, in the investigator's judgment, will put them at a risk of major adverse event during this trial, are expected to progress during the study, or will interfere with safety and efficacy assessments. Initiation of new behavioral therapies for stuttering within 10 weeks prior to baseline. Use of antipsychotic drug therapy within 14 days prior to receiving treatment until the EoT visit. Participation in another clinical study with an IP administered in the last 30 days. Participants with a known hypersensitivity to NOE-105 or any of the excipients of the product. Patient must not intend to use cannabinoids, cocaine, or nonprescribed opiates. Involvement in the planning and/or conduct of the study (applies to both Noema staff and/or staff at the study site). Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements. Previous randomization in the present study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active<br>Escalating doses of NOE-105 capsules | Drug: NOE-105<br>* Escalating dose levels of NOE-105 will be given and maximum tolerated dose will be maintained<br>* Other names: Escalating dose levels of NOE-105;|
| Placebo Comparator: Placebo<br>Escalating doses of matching placebo | Drug: Placebo<br>* Escalating dose levels of matching Placebo will be given<br>* Other names: Placebo to match;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to end point in severity subset of the MLGSSS | MLGSSS refers to Maguire-Leal-Garibaldi Self-rated Stuttering Scale | Up to 71 days | 
| Number of participants with adverse events | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment | Up to 71 days | 
| Severity of the adverse events | Adverse events will be categorized as mild, moderate or severe by the investigator | Up to 71 days | 
| Change in the hematological parameters | Platelet count, RBC count, Hemoglobin, hematocrit and differential WBC count will be assessed | Up to 71 days | 
| Change in clinical chemistry | Urea, creatinine, potassium, SGOT, SGPT, glucose, sodium chloride, magnesium, phosphates, calcium, total and conjugated bilirubin, GGT, total protein albumin, phosphokinase, and plasma prolactin will be assessed | Up to 71 days | 
| Change in the vital signs | Temperature, weight, height, pulse rate and blood pressure will be assessed. | Up to 71 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to end point in SDS | SDS refers to Sheehan disability scale | Up to 71 days | 
| PGI-S rating at end point | PGI-S refers to patient global impression of severity | Up to 71 days | 
| CGI-C rating at end point | Clinician global impression of change | Up to 71 days | 
| Rating of the medication satisfaction questionnaire at end point | To evaluate the patient's satisfaction in treatment with NOE-105 | Up to 71 days | 
| Change from baseline to end point in clinician-rated stuttering severity instrument-4 | To evaluate the effect of NOE-105 on the change in stuttering severity | Up to 71 days | 
| PGI-C rating at end point | PGI-C refers to patient global impression of change | Up to 71 days | 
| Change in mood as rated by the patient through change from baseline to end point in Quick inventory of depressive symptomology (QIDS-16) |  | Up to 71 days |