A Study in Healthy Subjects to Assess the Safety, Tolerability and Pharmacokinetics of HTL0022562

Study Overview
=================
Brief Summary
-----------------
Phase 1, randomised, double-blind, first in human, two part, single centre, placebo controlled, single and multiple ascending dose trial in healthy adult subjects to evaluate the safety, tolerability and pharmacokinetics of HTL0022562.

Detailed Description
-----------------
This is a first in human, two part, double blind, placebo controlled, randomised single and multiple ascending subcutaneous dose study to evaluate the safety, tolerability and pharmacokinetics of HTL0022562. Part 1 comprises of 7 sequential ascending dosing cohorts and Part 2 comprises of 4 multiple ascending dosing cohorts.

Official Title
-----------------
A Phase 1, Randomised, Double-Blind, Placebo-Controlled, First in Human Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses of Subcutaneous HTL0022562 in Healthy Adult Subjects

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Drug: HTL0022562
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: Healthy males or healthy females (WoNCBP) aged 18 to 55 years inclusive, with a body mass index 18.5-30kgm2 and body weight less than 50kg. Healthy on the basis of a clinical history, physical examination, electrocardiogram (ECG), vital signs and laboratory tests of blood and urine. Willingness to comply with requirements or the trial, including contraception requirements. Able to give fully informed consent. Key Exclusion Criteria: Confirmed current COVID 19 infection before randomisation. Clinical signs and symptoms consistent with COVID 19 (e.g. fever, dry cough, dyspnoea, sore throat, or fatigue) or confirmed infection by appropriate laboratory test within the last 4 weeks prior to Screening or on admission. Suffered from severe course of COVID 19 (ECMO, mechanically ventilated). Receipt of any IMP in a clinical research study within the previous 3 months (or 5 half-lives, whichever is longer) of Screening. Any abnormalities on 12-lead ECG or BP at Screening (as specified). History of any drug or alcohol abuse in the past 2 years. Vital signs outside the normal range for healthy volunteers Clinically significant abnormal biochemistry, haematology, coagulation, or urinalysis Abnormal renal function, hepatic function or history of abnormal hepatic function occurring during treatment with investigational or licensed drugs, which led to permanent discontinuation of treatment. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (anti HCV), or human immunodeficiency virus (HIV) History of clinically significant cardiovascular, renal, hepatic, chronic respiratory or gastrointestinal disease, neurological or psychiatric disorder, or current hepatic renal dysfunction as judged by the investigator. Risk factor for ischaemic heart disease or cerebrovascular disease. Failure to satisfy, in the Investigator's judgement, the subject's fitness to participate for any other reason, including previous serious adverse reaction or serious hypersensitivity reactions to any drug or formulation excipients administered parenterally or orally. All female subjects must have a negative serum and urine pregnancy test at Screening and admission, respectively.

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1 Single Ascending Dose<br>Eight subjects in up to 7 cohorts will be dosed. One or more subcutaneous injections of HTL0022562 will be administered. In each cohort, 6 subjects will receive HTL0022562 and 2 subjects will receive placebo. | Drug: HTL0022562<br>* HTL0022562<br>Drug: Placebo<br>* Placebo<br>|
| Experimental: Part 2 Multiple Ascending Dose<br>Eight subjects in up to 4 cohorts will be dosed, following safety, tolerability and PK review of completed dose of Single Ascending Dose Cohort 5. In each cohort, 6 subjects will receive HTL0022562 and 2 subjects will receive placebo. | Drug: HTL0022562<br>* HTL0022562<br>Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Treatment Emergent Adverse Events (TEAEs) | All AEs, including clinical laboratory, vitals signs, body temperature, respiratory rate, physical examinations, local tolerability and site injection reactions, and ECGs will be analyzed in all subjects. | Screening up to post last dose: Day 8 (Part 1) / Day 15 (Part 2) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1 and Part 2: Cmax | Plasma pharmacokinetic parameter: maximum systemic concentration of HTL0022562 | Part 1 up to Day 8, Part 2 up to Day 15 | 
| Part 1 and Part 2: Tmax | Plasma pharmacokinetic parameter: time to Cmax of HTL0022562 Plasma pharmacokinetic parameter: time to Cmax of HTL0022562 | Part 1 up to Day 8, Part 2 up to Day 15 | 
| Part 1 and Part 2: Area Under Curve (AUC) | Plasma pharmacokinetic parameter: Area under the plasma concentration versus time curve derived from systemic concentrations of HTL0022562 | Part 1 up to Day 8, Part 2 up to Day 15 | 
| Part 1 and Part 2: Ae | Urine pharmacokinetic parameter: Amount of HTL0022562 recovered in urine for each urine collection interval | Part 1 up to Day 8, Part 2 up to Day 15 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
First in Human, Single Ascending Dose, Multiple Ascending Dose