Phase I Study of Colistin Methanesulfonate Sodium
- Conditions
- Infections, Pseudomonas
- Interventions
- Drug: Saline
- Registration Number
- NCT01449838
- Lead Sponsor
- GlaxoSmithKline
- Brief Summary
This is a clinical study protocol for a single centre, randomized, double blind, placebo controlled, single and repeat dose study to investigate the safety, tolerability and pharmacokinetics of intravenous dosing of Colistin Methanesulfonate Sodium (CMS-Na) in healthy Japanese male subjects.
Eighteen subjects will receive CMS-Na 2.5mg/kg (as colistin activity or 75,000 IU/kg) or placebo as a single dose and twice daily for 2.5 days by intravenous infusion.
Blood and urine samples for pharmacokinetics analysis will be taken at regular intervals after dosing. Safety will be assessed by measurement of vital signs, Echocardiogram (ECGs), safety laboratory data, renal function and review of adverse events.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 22
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Saline Saline Subjects were administered single dose or twice daily for 2.5 days repeat dose of placebo by the intravenous route. Colistimethate sodium Colistimethate sodium 2.5 milligrams (mg)/kilogram (kg) of CMS-NA (as colistin activity or 75,000 International Unit/kg) was administered as single dose or twice daily for 2.5 days repeat dose by the intravenous route.
- Primary Outcome Measures
Name Time Method Profile of safety (repeat day1 and 2) Vital: pre-dose, 2,4,8,12 and14h after the start of infusion. ECGs: pre-dose and 12h after the start of infusion. Clinical lab: pre-dose. Adverse event: All study period. Vital signs, ECGs, clinical laboratory test and adverse events.
Profile of safety (repeat day 3) Vital: pre-dose, 2,4,8,12,24,36,48h after the start of infusion. ECGs: pre-dose, 12, 24, 36 and 48h after the start of infusion. Clinical lab: pre-dose, 24 and 48h after the start of infusion. Adverse event: All study period. Vital signs, ECGs, clinical laboratory test and adverse events.
Profile of pharmacokinetics (PK) Single dose and repeat dose day 3: pre-dose, 15min (m), 30m, 35m, 1,2,4,6,8,12,16,24,36 and 48h after the start of infusion. Repeat dose day 1 and day 2: pre-dose and 12h after the start of infusion. Maximum drug concentration (Cmax), Time of occurrence of Cmax (tmax), Terminal phase half-life(t1/2), Area under the concentration-time curve: AUC(0-inf), AUC(0-12), AUC(0-last), Clearance (CL), Fraction of urinary excretion (fe), Accumulation ratio (Ro and Rs).
Profile of renal function Single and repeat dose day 3: Pre-dose, 12, 24 36 and 48h after the start of infusion. Repeat dose day 1 and day 2:Pre-dose and 12h after the start of infusion. CLcr urine sampling: -24-0h of start of single dose and 24-36, 36-48h after d3 repeat dose Urinary β2-microglobulin, N-acetyl-β-D-glucosaminidase and creatinine clearance (CLcr).
Profile of safety (single) Vital: -24h, pre-dose, 2,4,8,12,24,36,48h after the start of infusion. ECGs: -24h, pre-dose, 12, 24, 36 and 48h after the start of infusion. Clinical lab: pre-dose, 24 and 48h after the start of infusion. Adverse event: All study period. Vital signs, ECGs, clinical laboratory test and adverse events.
- Secondary Outcome Measures
Name Time Method Profile of other PK Single dose and repeat dose day 3: pre-dose, 15m, 30m, 35m, 1,2,4,6,8,12,16,24,36 and 48h after the start of infusion. Repeat dose day 1 and day 2: pre-dose and 12h after the start of infusion. AUC(0-24), %AUCex, rambda_z, Volume of destribution based on the terminal phase (Vz) and volume of distribution at steady state (Vss)
Profile of urinary PK Single dose and repeat dose day 3: 0-2, 2-4, 4-6, 6-12, 12-18, 18-24, 24-30, 30-36, 36-42, 42-48h. Repeat dose day 1 and day 2: Every 6 hours. Urinary recovery (Ae) and Renal clearance (CLr)
Trial Locations
- Locations (1)
GSK Investigational Site
🇦🇺Randwick, New South Wales, Australia