Safety, Tolerability and PK of PXL770 in Healthy Male Subjects

Study Overview
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Brief Summary
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PXL770 is a direct activator of 5' adenosine monophosphate-activated protein kinase (AMPK) being developed by Poxel S.A. for the treatment of type 2 diabetes mellitus (T2DM). In Part A of this study, we'll test the safety, tolerability and pharmacokinetics (PK) of repeated doses. In Part B, we'll co-administer PXL770 and rosuvastatin (a HMG-CoA reductase inhibitor) to assess any drug-drug interaction.

Official Title
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A Double-blind, Randomised, Placebo-controlled Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Ascending Doses of PXL770, Including an Open-label, One-sequence Part to Assess the Drug-drug Interaction With Rosuvastatin in Healthy Male Subjects

Conditions
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Metabolic Disease

Intervention / Treatment
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* Drug: PXL770
* Drug: Placebo
* Drug: Rosuvastatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male subjects deemed healthy on the basis of a clinical history, physical examination, ECG, vital signs, and laboratory tests of blood and urine body mass index in the range 18.5-29.9 kg/m² body weight at least 60 kg willing to use reliable contraception able to give fully informed written consent. Exclusion Criteria: Pregnant or lactating woman, or sexually active woman of child-bearing potential not using reliable contraception Clinically relevant abnormal findings at the screening assessment Clinically significant vital signs outside the acceptable range at screening Clinically relevant abnormal medical history, surgery or concurrent medical condition Acute or chronic illness Estimated glomerular filtration rate less than 80 mL/min/1.73 m2 Severe adverse reaction to any drug or sensitivity to the trial medication or its components Significant food allergy; vegetarian or vegan Participation in other clinical trials of unlicensed or prescription medicines, or loss of more than 400 mL blood, within the 3 months before first dose of trial medication Drug or alcohol abuse Smoking of more than 5 cigarettes daily Possibility that subject will not cooperate Positive test for hepatitis B & C, HIV Objection by a General Practitioner

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

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A1<br>Dose 1 or placebo | Drug: PXL770<br>* MAD<br>Drug: Placebo<br>* MAD<br>|
| Experimental: Group A2<br>Dose 2 or placebo | Drug: PXL770<br>* MAD<br>Drug: Placebo<br>* MAD<br>|
| Experimental: Group A3<br>Dose 3 or placebo | Drug: PXL770<br>* MAD<br>Drug: Placebo<br>* MAD<br>|
| Experimental: Group A4<br>Dose 4 or placebo | Drug: PXL770<br>* MAD<br>Drug: Placebo<br>* MAD<br>|
| Experimental: Group A5<br>Dose 5 or placebo | Drug: PXL770<br>* MAD<br>Drug: Placebo<br>* MAD<br>|
| Experimental: Group B<br>Dose + Rosuvastatin | Drug: PXL770<br>* MAD<br>Drug: Rosuvastatin<br>* DDI<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: PK parameters of PXL770 after repeated doses Part B: PK parameters of rosuvastatin before and after repeated doses of PXl770 | - Cmax: peak plasma concentration after dosing | From baseline to day 14 | 
| Part A: PK parameters of PXL770 after repeated doses | - AUC0-t: area under the concentration-time curve from 0 extrapolated to time t | From baseline to day 14 | 
| Part A: PK parameters of PXL770 after repeated doses | - AUC0-∞: area under the concentration-time curve from 0 extrapolated to infinite | From baseline to day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | Incidence of treatment emergent adverse events | From baseline to day 14 |