A Phase 1 Study in Healthy Volunteers to Evaluate the Safety, Tolerability and Pharmacokinetics of AVLX-144

Study Overview
=================
Brief Summary
-----------------
This is a randomised, double-blind, placebo-controlled, single ascending dose study in healthy volunteer subjects. Each dose level will be investigated with eight 20-50-year-old male subjects (6 on active drug and 2 on placebo). Additionally, eight healthy elderly subjects (65-80 years of age, males and females), 6 on active drug and 2 on placebo, will be included in the study at one dose level, once the safety and tolerability of AVLX-144 has been documented in younger subjects.

Official Title
-----------------
A Phase 1, Randomised, Double-blind, Placebo-controlled, Single Ascending Dose Study in Healthy Volunteers to Evaluate the Safety, Tolerability and Pharmacokinetics of Intravenously Administered AVLX-144

Conditions
-----------------
Safety Issues, Tolerance

Intervention / Treatment
-----------------
* Drug: AVLX-144
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: - Healthy male and female subjects, body mass index (BMI) 18-28 kg/m2, body weight from 50 kg (females) or 60 kg (males) up to 100 kg, good general health. Exclusion Criteria: - History or evidence of current clinically significant cardiovascular, pulmonary, renal, hepatic, gastrointestinal, haematological, metabolic-endocrine, neurological, urogenital or psychiatric disorder. Febrile convulsions in childhood do not necessarily exclude a subject, but subjects with any type of generalized seizure in adulthood must be excluded. Personal or first-degree family history of congenital long QT syndrome or sudden death of a first-degree relative suspected to be due to long QT syndrome will also exclude the subject.

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 80 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: Cohort 1<br>AVLX-144_dose1 | Drug: AVLX-144<br>* Test drug<br>* Other names: Test drug;Drug: Placebo<br>* Placebo<br>|
| Experimental: Cohort 2<br>AVLX-144_dose2 | Drug: AVLX-144<br>* Test drug<br>* Other names: Test drug;Drug: Placebo<br>* Placebo<br>|
| Experimental: Cohort 3<br>AVLX-144_dose3 | Drug: AVLX-144<br>* Test drug<br>* Other names: Test drug;Drug: Placebo<br>* Placebo<br>|
| Experimental: Cohort 4<br>AVLX-144_dose4 | Drug: AVLX-144<br>* Test drug<br>* Other names: Test drug;Drug: Placebo<br>* Placebo<br>|
| Experimental: Cohort 5<br>AVLX-144_dose5 | Drug: AVLX-144<br>* Test drug<br>* Other names: Test drug;Drug: Placebo<br>* Placebo<br>|
| Experimental: Cohort 6<br>AVLX-144_elderly | Drug: AVLX-144<br>* Test drug<br>* Other names: Test drug;Drug: Placebo<br>* Placebo<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of AVLX-144 | Safety and tolerability will be assessed by recording adverse events (AEs), by performing physical examinations and safety laboratory assessments (blood and urine), and by recording vital signs and electrocardiograms (ECGs). | From randomisation to end of study participation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics parameter | AUClast (the area under the plasma concentration-time curve from time zero to the last sample with a quantifiable concentration) | From dosing until 48 hours after dosing | 
| Pharmacokinetics parameter | AUC0-24 (the area under the plasma concentration-time curve from time zero to 24 h), | 24 hrs | 
| Pharmacokinetics parameter AUC | AUCinf (the area under the plasma concentration-time curve from time zero extrapolated to infinity, if feasible) | From start to end of assessment | 
| Pharmacokinetics parameter elimination | elimination constant λz and t½ (terminal elimination half-life, if feasible), and systemic plasma clearance (Cl) and volume of distribution (Vd) | From start to end of assessment |