Pharmacokinetics Study of XG005 Capsule

A Phase 1, Single-Center, Randomized, Placebo-Controlled, Ascending Single-Dose Study of the Pharmacokinetics, Safety, and Tolerability of Oral XG005 in Healthy Volunteers

This was a Phase 1, single-center, randomized, placebo-controlled, 2-period, ascending single-dose study assessing the PK, safety, and tolerability of single ascending doses of XG005 (Period 1) and the naproxen and pregabalin combination (Period 2), in 5 dose groups each with 10 subjects.

Study Overview

• Status: Completed
• Conditions: Pain
• Intervention / Treatment: Drug: XG005; Drug: Combination of Naproxen and Pregabalin; Drug: Placebos

Detailed Description

Period 1 was double-blind and randomized 8 subjects (1:1 allocation ratio by gender) to XG005 and 2 subjects (1:1 allocation ratio by gender) to placebo. Subjects were enrolled sequentially into a total of 5 ascending dose levels pending safety review, and PK review where possible, of Period 1 of the prior dose level. Sentinel dose participants (1 for XG005 and 1 for placebo) were included as the first dose administered at each dose level in Period 1.

In Period 2, all subjects in the last three XG005 dose groups received approximate molar equivalents of naproxen and pregabalin corresponding to XG005 doses after a 7-day washout period. Period 2 was open-label with 10 subjects per group.

PK blood samples in each treatment period were collected at 0 (pre-dosing), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hrs after drug administration.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Linear Clinical Research Ltd

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• BMI range of 18-30 kg/m2
• Medically healthy subjects
• Creatinine clearance ≥ 80 mL/min

Exclusion Criteria:

• History or presence of significant diseases
• History or presence of alcoholism or drug abuse
• Consumption of alcohol 48 hours prior each dose
• Hypersensitivity or idiosyncratic reaction to the study drug
• Abnormal diet (for whatever reason) during the 30 days prior to the first dosing;
• Donation (standard donation amount or more) of blood or blood products
• Plasma donation within 7 days prior to the study;
• Participation in another clinical trial within 30 days prior to the first dose;
• Female subjects who are pregnant or lactating;
• Hemoglobin < 120 g/L

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Period 1- XG005; XG005 capsule in 4 dose level	Drug: XG005; XG005 Capsule
Active Comparator: Period 2- Naproxen and Pregabalin; Combination of Naproxen and Pregabalin	Drug: Combination of Naproxen and Pregabalin; Naproxen and Pregabalin are commercially available products with trade names of Aleve and Lyrica
Placebo Comparator: Period 1- Placebo; XG005 matching placebo	Drug: Placebos; Placebo Capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum concentration (Cmax)	Day1 to Day 4
Time to maximum concentration (Tmax)	Day1 to Day 4
Area under the concentration-time curve from time 0 to last measurable time-point (AUC0-t)	Day1 to Day 4
Area under the concentration-time curve from time 0 to infinity (AUC0-inf)	Day1 to Day 4
Terminal Elimination Rate Constant (kel)	Day1 to Day 4
Terminal half-life (t1/2)	Day1 to Day 4
Terminal clearance (CL/F)	Day1 to Day 4
Volume of distribution (Vd/F)	Day1 to Day 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
incidence and severity of adverse events (AEs)		Day -1 to Day 8
blood pressure	vital signs	Day -1 to Day 8
heart rate	vital signs	Day -1 to Day 8
respiratory rate	vital signs	Day -1 to Day 8
temperature	vital signs	Day -1 to Day 8
physical examination	Cardiovascular, Ears, Nose and Throat, Eyes, Gastrointestinal, Head, Lymph Nodes, Musculoskeletal, Neurological, Respiratory, Skin	Day -1 to Day 8
electrocardiogram (ECG) parameters;	ECG-PR, RR, QRS, QT, and QTc intervals	Day -1 to Day 8
clinical laboratory parameters -chemistry	BUN, Creatinine, Total bilirubin, Total protein, Alkaline phosphatase, Uric Acid, Estimated creatinine clearance, Creatine Phosphokinase (CPK), AST (SGOT), ALT (SGPT), Glucose, Sodium, Potassium	Day -1 to Day 8
clinical laboratory parameters- hematology	Hemoglobin, Hematocrit, Red Blood Cell Count, White Blood Cell Count with differential, Platelet Count	Day -1 to Day 8
clinical laboratory parameters urinalysis	pH • Specific gravity • Protein; Glucose • Ketones • Bilirubin; Blood • Nitrite • Urobilinogen; Leukocytes	Day -1 to Day 8

Collaborators and Investigators

• Sponsor: Xgene Pharmaceutical Pty Ltd

Study record dates

Study Major Dates

• Study Start (Actual): October 16, 2017
• Primary Completion (Actual): January 18, 2018
• Study Completion (Actual): March 19, 2018

Study Registration Dates

• First Submitted: July 13, 2020
• First Submitted That Met QC Criteria: July 30, 2020
• First Posted (Actual): August 5, 2020

Study Record Updates

• Last Update Posted (Actual): August 18, 2020
• Last Update Submitted That Met QC Criteria: August 14, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anti-Anxiety Agents; Anticonvulsants; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Gout Suppressants; Pregabalin; Naproxen
• Other Study ID Numbers: XG005-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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