First-in-Human study of RGH-338

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 200

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.
4. Healthy as determined by a responsible physician, based on medical, surgical and psychiatric history at screening, and physical examination, vital signs, clinical laboratory tests and 12-lead safety ECG at both screening and admission.
5. Non-smokers or subjects who have not smoked (or used any nicotine products) for at least 3 months before screening; negative cotinine test at screening and admission.
6. Agree to use effective contraception method and agree to not donate sperm, and not have their partner become pregnant or contact with sperm, throughout the study and for up to 3 months after the last administration of the IMP.
7. Agree not to donate blood or blood products during the study and for up to 3 months after the administration of the trial medication.
8. Sufficient intelligence to understand the nature of the trial and any hazards of participating in it, as judged by the Investigator. Ability to communicate satisfactorily with the Investigator and to participate in, and comply with the requirements of, the entire trial.
9. Willingness to give written consent to participate after reading the information and consent form, and after having the opportunity to discuss the trial with the Investigator or their delegate.
10. Willingness to give written consent to have data entered into Verified Clinical Trials”.
11. Agree to avoid sunbathing or using a sunbed during the trial.
12. Agree to avoid any strenuous exercise from screening until follow-up.

Exclusion Criteria

1. Clinically relevant abnormal history, physical finding,12-lead safety ECG 12-lead safety ECG (e.g. PQ/PR interval > 210 ms , presence of Left Bundle Branch Block (LBBB), AV Block (second degree or higher), or a permanent pacemaker or implantable cardioverter defibrillator [ICD]), 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.
3. Personal history or presence of epilepsy, seizures, recent head trauma, severe head injury, unexplained blackouts, childhood febrile seizures, chronic pain or any other clinically significant chronic neurological condition or any clinically significant psychiatric disorder (including but not limited to diagnosed anxiety disorders or depression).
4. (Parts 1 and 3) History or current significant ophthalmologic or neurologic condition that would adversely affect the eye movement assessments.
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.
6. Diagnosis or suspicions of any sleep disorder in the last 6 months or current complaints of sleep disturbance or daytime symptoms attributable to unsatisfactory sleep. Shift workers (those whose routine work hours overlap with the typical sleep period).
7. Clinically relevant history or presence of respiratory, gastrointestinal (including lactose intolerance), renal, hepatic (including Gilbert’s syndrome), haematological, lymphatic, cardiovascular (including recurrent orthostatic hypotension, syncope, vasovagal attacks), musculoskeletal (including clinically relevant history or presence of muscular disorder),
genitourinary, immunological, dermatological, connective tissue diseases or disorders sufficient to invalidate the volunteer’s participation in the trial or make it unnecessarily hazardous.
8. QTc values measured at screening visit greater than 450 ms or lower than 340 ms on 12- lead ECG, using Fridericia’s formula (QTcF) for correction. Triplicate measurements will be made at screening and predose, and any out-of-range reading on mean QTcF higher than 450 ms (M) will lead to exclusion.
9. Family history of long QT syndrome or sudden death.
10. Surgical history (e.g. stomach bypass) or medical condition that might affect absorption of medicines.
11. A history of any kind of hypersensitivity (eg. Drugs/excipients) or allergic reactions to any of the inactive ingredients contained in the active or placebo drug products, including compounds related to RGH-338.
12. Abnormal vital signs at screening or admission, after 5 minutes of rest in supine position, outside the following ranges:
-systolic blood pressure 90–140 mmHg;
-diastolic blood pressure 50–90 mmHg;
-pulse rate 45–100 beats/minute;
-tympanic temperature 35.4–37.8 °C;
-respiratory rate 8-20 breaths/min.
Borderline values (i.e. values that are above or below the criterion’s defined range with 5 mmHg for blood pressure, 5 beats/min for pulse rate and 0.2 °C for body temperature) have to be repeated. Subjects can be included if the repeat value is within the range or still in the borderline range but deemed not clinically significant by the Investigator. For all other out of range vitals one repeat is allowed.
13. Clinically significant elevated values at screening or admissio

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Tolerability / safety endpoints<br>Safety: vital signs, 12-lead safety ECG, physical examination, laboratory safety tests (routine haematology, biochemistry, urinalysis<br>and coagulation), C-SSRS, concomitant medication and adverse events.<br>Tolerability: adverse events.<br><br>Pharmacokinetic endpoints<br>The following pharmacokinetic parameters of RGH-338 will be determined as applicable.<br>Part 1: Cmax, Tmax, AUC0-t, AUC0-24, AUCinf, MRT, CL/F, VZ/F, t1/2.<br>Part 2: Cmax, Tmax, AUC0-t, AUC0-24, AUCinf, MRT, CL/F, VZ/F, t1/2<br>Part 3: Cmax, Tmax, AUC0-t, AUC0-24 and AUCtau will be determined for the first day of multiple dosing. For the last day of multiple<br>dosing Cmax, Tmax, Cmin, Cavg, AUC0-t, AUCtau, AUC0-24, AUCinf, MRT, CL/F, V/F, t1/2 and Fluctuation% will be calculated.<br>Renal clearance and the cumulative amount of RGH-338 excreted in urine will be determined, if applicable.

Secondary Outcome Measures