Safety, Tolerability and PK of PXL770 in Healthy Male Subjects

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

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.

Study Overview

• Status: Completed
• Conditions: Metabolic Disease
• Intervention / Treatment: Drug: PXL770; Drug: Placebo; Drug: Rosuvastatin

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom
    • Hammersmith Medicines Research (HMR)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Poxel SA

Study record dates

Study Major Dates

• Study Start (Actual): August 21, 2017
• Primary Completion (Actual): March 16, 2018
• Study Completion (Actual): March 16, 2018

Study Registration Dates

• First Submitted: November 6, 2017
• First Submitted That Met QC Criteria: January 9, 2018
• First Posted (Actual): January 10, 2018

Study Record Updates

• Last Update Posted (Actual): August 24, 2018
• Last Update Submitted That Met QC Criteria: August 23, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rosuvastatin Calcium
• Other Study ID Numbers: PXL770-002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No