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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 | Experimental | AVLX-144_dose1 |
|
| Cohort 2 | Experimental | AVLX-144_dose2 |
|
| Cohort 3 | Experimental | AVLX-144_dose3 |
|
| Cohort 4 | Experimental | AVLX-144_dose4 |
|
| Cohort 5 | Experimental | AVLX-144_dose5 |
|
| Cohort 6 | Experimental | AVLX-144_elderly |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AVLX-144 | Drug | Test drug |
|
| 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 |
| 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 |
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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.
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| Name | Affiliation | Role |
|---|---|---|
| Mika Scheinin, MD | Clinical Research Services Turku - CRST Oy | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Research Services Turku / CRST Oy | Turku | Finland |
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| ID | Term |
|---|---|
| D004341 | Drug Evaluation |
| ID | Term |
|---|---|
| D000076722 | Drug Development |
| D008919 | Investigative Techniques |
| D005069 | Evaluation Studies as Topic |
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| Placebo | Drug | Placebo |
|
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 |