Pharmacokinetics Study of XG005 Capsule

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Pain

Intervention / Treatment
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* Drug: XG005
* Drug: Combination of Naproxen and Pregabalin
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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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

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

Sexes Eligible for Study
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All

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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Period 1: ascending single-dose of XG005 vs Placebo; Period 2: combination of Naproxen and Pregabalin
Masking: Double


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 |