Autism spectrum disorder
Conditions
Interventions
RGH-338 or placebo (oral tablets) , starting dose of 0.05 mg in cohort 1 of
Part 1, subsequent dose levels are to be determined following satisfactory
review of the safety, tolerability, pharmacodyn
Sponsors
Gedeon Richter Plc.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Healthy male volunteers. 2. Aged 18*45 years (inclusive). 3. A body mass index (Quetelet index) in the range 18.5 * 30.0 kg/m2 (inclusive) as measured at screening.
Exclusion criteria
Exclusion criteria: 1. Clinically relevant abnormal history, physical finding,12-lead safety ECG, or laboratory value at screening that could interfere with the objectives of the trial or the safety of the volunteer. 2. Family history of seizures or a clinically significant psychiatric disorder. 5. Risk of suicide, as judged by an Investigator, based upon available source information * including the C-SSRS or family history of suicide * indicating current suicidal ideation or a history of active suicidal ideation or suicide attempts. 28. Positive SARS-CoV-2 PCR analysis prior to first dosing. 29. Any current, clinically significant, known medical condition in particular any existing conditions that would affect sensitivity to cold (such as atherosclerosis, Raynaud*s disease, urticaria, hypothyroidism) or pain (such as disease that causes pain, hypesthesia, hyperalgesia, allodynia, paraesthesia, neuropathy). 30. Participants indicating pain tests intolerable at screening. Participants achieving tolerance at >80% of maximum input intensity for cold pressor and electrical pain tests are to be excluded. If pressure pain test tolerance is >80% of maximum input intensity they may be enrolled as per PI judgement.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Tolerability / safety endpoints Safety: vital signs, 12-lead safety ECG, physical examination, laboratory safety tests (routine haematology, biochemistry, urinalysis and coagulation), C-SSRS, concomitant medication and adverse events. Tolerability: adverse events. Pharmacokinetic endpoints The following pharmacokinetic parameters of RGH-338 will be determined as applicable Part 1: Cmax, Tmax, AUC0-t, AUC0-24, AUCinf, MRT, CL/F, VZ/F, t1/2. Part 2: Cmax, Tmax, AUC0-t, AUC0-24, AUCinf, MRT, CL/F, VZ/F, t1/2 Part 3: For the first day of multiple dosing: Cmax, Tmax and AUCtau. For the last day of multiple dosing: Cmax, Tmax, Cmin, Cavg, AUC0-t, AUCtau, AUCinf, MRT, CL/F, V/F, t1/2, Fluctuation%, Rac. Renal clearance and the cumulative amount of RGH-338 excreted in urine will be determined, if applicable. | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacodynamic endpoints Part 1: 1. Heart rate corrected QT interval measured with 12-lead Holter ECG for precision QT analysis. 2. Changes in subjective sleep pattern assessed with Leeds Sleep Evaluation Questionnaire (LSEQ). 3. The NeuroCart CNS battery test will include the following core assessments to characterize RGH-338*s pharmacodynamic profile in SAD. 4. Dynamo hand-held dynamography (HHD) 5. Plasma growth hormone levels. Part 3: 1. Heart rate corrected QT interval measured with 12-lead Holter ECG for precision QT analysis. 2. Changes in subjective sleep pattern assessed with Leeds Sleep Evaluation Questionnaire (LSEQ) 3. Polysomnography (PSG) will include, among others, the following parameters for analysis: 4. The NeuroCart CNS battery test consists of several assessments to characterize the pharmacodynamic profile of RGH-338 in parts 1 and 3. 5. The PainCart battery test (in Part 3) consists of several assessments to characterize the effect of RGH-338 on nociceptive (pain) detection and tolerance threshold 6. Dynamo hand-held dynamography (HHD) 7. Plasma growth hormone as a peripheral neuroendocrine biomarker for GABAB receptor engagement. | — |
Countries
Netherlands
Outcome results
None listed