Pain
Conditions
Brief summary
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
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.
Interventions
DRUGXG005
XG005 Capsule
DRUGCombination of Naproxen and Pregabalin
Naproxen and Pregabalin are commercially available products with trade names of Aleve and Lyrica
DRUGPlacebos
Placebo Capsule
Sponsors
Xgene Pharmaceutical Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Masking description
Period 1: Participants and investigators were blinded Period 2: Open label
Intervention model description
Period 1: ascending single-dose of XG005 vs Placebo; Period 2: combination of Naproxen and Pregabalin
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| 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
| Measure | Time frame | Description |
|---|---|---|
| clinical laboratory parameters- hematology | Day -1 to Day 8 | Hemoglobin, Hematocrit, Red Blood Cell Count, White Blood Cell Count with differential, Platelet Count |
| incidence and severity of adverse events (AEs) | Day -1 to Day 8 | — |
| clinical laboratory parameters urinalysis | Day -1 to Day 8 | * pH • Specific gravity • Protein * Glucose • Ketones • Bilirubin * Blood • Nitrite • Urobilinogen * Leukocytes |
| blood pressure | Day -1 to Day 8 | vital signs |
| heart rate | Day -1 to Day 8 | vital signs |
| respiratory rate | Day -1 to Day 8 | vital signs |
| temperature | Day -1 to Day 8 | vital signs |
| physical examination | Day -1 to Day 8 | Cardiovascular, Ears, Nose and Throat, Eyes, Gastrointestinal, Head, Lymph Nodes, Musculoskeletal, Neurological, Respiratory, Skin |
| electrocardiogram (ECG) parameters; | Day -1 to Day 8 | ECG-PR, RR, QRS, QT, and QTc intervals |
| clinical laboratory parameters -chemistry | Day -1 to Day 8 | BUN, Creatinine, Total bilirubin, Total protein, Alkaline phosphatase, Uric Acid, Estimated creatinine clearance, Creatine Phosphokinase (CPK), AST (SGOT), ALT (SGPT), Glucose, Sodium, Potassium |
Countries
Australia
Outcome results
None listed