Phase I study in healthy volunteers of a treatment to improve/or normalize symptoms and deficits in patients with rare neurological disorders associated with reduced Kv3 channel function Not Applicable
Conditions
Interventions
Subjects will be numbered consecutively, in the order in which they arrive on the ward and are entered into the trial. Subject numbers will be allocated to treatment sequences (active or placebo) acco
enrollment of up to three groups of 8 men:
Part A, Group 1, Session 1: 6 AUT00201 Active, 2 AUT00201 matching placebo
Part A, Group 1, Session 2: 6 AUT00201 Active, 2 AUT00201 matching placebo
Part
Sponsors
Autifony Therapeutics (United Kingdom)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Healthy male volunteer (groups other than Part A2) or healthy female volunteer (Part A2) 2. Aged 18–45 years (men) or 18–65 years (women) 3. A body mass index (BMI; Quetelet index) in the range 18.0–31.0 4. Sufficient intelligence to understand the nature of the trial and any hazards of participating in it. Ability to communicate satisfactorily with the investigator and to participate in, and comply with the requirements of, the entire trial 5. 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 his delegate 6. Agree to use effective contraception 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. Registered with a General Practitioner (GP) in the UK 9. Willingness to give written consent to have data entered into The Overvolunteering Prevention System (TOPS)
Exclusion criteria
Exclusion criteria: 1. Woman who is pregnant or lactating, or woman of child-bearing potential who is sexually active and not using a highly effective method of contraception (see section 11) 2. Clinically relevant abnormal history, physical findings, ECG, Holter, or laboratory values at the pre-trial screening assessment that could interfere with the objectives of the trial or the safety of the volunteer 3. Presence of acute or chronic illness or history of chronic illness sufficient to invalidate the volunteer’s participation in the trial or make it unnecessarily hazardous. 4. Family history of seizures and history of seizures or recent head trauma. History or presence of epilepsy, severe head injury, unexplained blackouts, childhood febrile seizures, chronic pain or any other chronic neurological condition or any psychiatric disorder (including but not limited to diagnosed anxiety disorders or depression, family history of suicide, history of attempted suicide, etc) 5. Abnormal safety EEG at screening (Part A1 only) 6. Impaired endocrine, thyroid, hepatic, respiratory or renal function, diabetes mellitus, coronary heart disease, or history of any psychotic mental illness 7. Surgery (eg stomach bypass) or medical condition that might affect the absorption of medicines 8. Presence or history of severe adverse reaction to any drug 9. Use of a prescription medicine (except contraceptive implants in females) during the 28 days before the first dose of trial medication or use of an over-the-counter medicine, herbal treatments or dietary supplements (including St John’s Wort), with the exception of acetaminophen (paracetamol) or multivitamins, during the 7 days before the first dose of trial medication 10. Receipt of an investigational product (including prescription medicines) as part of another clinical trial within the 3 months (or 5 half-lives, whichever is longer) before [first] admission to this study; in the follow-up period of another clinical trial at the time of screening for this study 11. Presence or history of drug or alcohol abuse, or intake of more than 21 units of alcohol weekly (for men) or 14 units of alcohol weekly (for women) or use of cigarettes or nicotine-containing products during the 3 months before the first dose until the end of the study 12. Blood pressure and heart rate in supine position at the screening examination outside the ranges: blood pressure 90–140 mm Hg systolic, 50–90 mm Hg diastolic; heart rate 40_100 beats/min. Borderline values (ie values that are = 5 mm Hg outside the relevant range for blood pressure, or 5 beats/min for heart rate) will be repeated. Subjects can be included if the repeat value is within range or still borderline, but deemed not clinically significant by the investigator 13. QT value, measured at the screening visit, greater than 450 msec for men or 470 msec for women on 12-lead ECG, using Fridericia’s formula (QTcF) for correction. Triplicate measurements will be made, and a mean QTcF value higher than 450 msec for men or 470 msec for women will lead to exclusion. A repeat (in triplicate) is allowed on one occasion for the determination of eligibility 14. Positive result for suicidal ideation or behaviour using the C-SSRS, including a positive response to items 3 to 5; or a history of suicidal behaviour in the past year 15. Possibility that the volunteer will not cooperate with the requirements of the protocol 16. Evidence of drug abuse on urine testing 17. Positive test for hepatitis B, hepatitis
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| PART A1 The tolerability of single oral doses of AUT00201 in healthy men is measured by collecting the percentage of subjects with treatment-related adverse events from Day 1 until the subject’s last visit PART A2 The tolerability of single doses of AUT00201 in healthy women is measured by collecting the percentage of subjects with treatment-related adverse events from Day 1 until the subject’s last visit PART A3 The tolerability of single oral doses of AUT00201 with food in healthy men is measured by collecting the percentage of subjects with treatment-related adverse events from Day 1 until the subject’s last visit. PART B The tolerability of repeated oral doses of AUT00201 in healthy men is measured by collecting the percentage of subjects with treatment-related adverse events from Day 1 until the subject’s last visit | — |
Secondary
| Measure | Time frame |
|---|---|
| PART A1 1. Pharmacokinetic (PK) profile of AUT00201 after single oral doses of AUT00201 in healthy men is measured from blood samples taken before and frequently up to 144 h 2. Effect of food on the bioavailability of single oral doses of AUT00201 in healthy men measured from blood samples taken before and frequently up to 144 h 3. Safety of AUT00201 in healthy men measured by collecting clinically significant changes to laboratory assessments (routine haematology, biochemistry and urinalysis), physical examinations, 12-lead ECG, 5-lead telemetry, 3-lead Holter monitoring, vital signs (supine and standing), and C-SSRS will be done frequently until the subject’s last visit. EEGs will be performed at baseline and 4 h post-dose and around 24 h PART A2 1. Pharmacokinetic (PK) profile of AUT00201 after single oral doses of AUT00201 in healthy women measured from blood samples taken before and frequently up to 144 h 2. Safety of AUT00201 in healthy women measured by collecting clinically significant changes to laboratory assessments (routine haematology, biochemistry and urinalysis), physical examinations, 12-lead ECG, 5-lead telemetry, 3-lead Holter monitoring, vital signs (supine and standing), and C-SSRS will be done frequently until the subject’s last visit. EEGs will be performed at baseline and 4 h post-dose and around 24 h PART A3 1. Pharmacokinetic (PK) profile of AUT00201 after single oral doses of AUT00201 in healthy men measured from blood samples taken before and frequently after dosing up to 144 h 2. Effect of food on the bioavailability of single oral doses of AUT00201 in healthy men measured from blood samples taken before and frequently after dosing up to 144 h 3. Safety of AUT00201 in healthy men measured by collecting clinically significant changes to laboratory assessments (routine haematology, biochemistry and urinalysis), physical examinations, 12-lead ECG, 5-lead telemetry, 3-lead Holter monitoring, vital signs (supine and standing), and C-SSRS | — |
Countries
England, United Kingdom
Contacts
Public ContactAlice Sharman
Outcome results
None listed