NCT01571661

A Double Blind, Randomized, Placebo Controlled, Single-dose Escalation, First-time-in-human Crossover Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Ascending Doses of GSK189075A in Healthy Subjects and in Subjects With Type 2 Diabetes Mellitus

Completed Phase 1 Last updated 3 April 2012

What this trial tests

Phase 1 trial testing GSK189075A in Diabetes Mellitus, Type 2 in 16 participants. Completed in 1 January 2005.

Timeline

1 September 2004

Primary endpoint
1 January 2005

1 January 2005

Quick facts

Lead sponsor	GlaxoSmithKline
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	basic science
Enrollment	16
Start date	1 September 2004
Primary completion	1 January 2005
Estimated completion	1 January 2005

Drugs / interventions tested

• GSK189075A — full drug profile →
• Placebo

Conditions studied

• Diabetes Mellitus, Type 2 — all drugs for Diabetes Mellitus, Type 2 →

Sponsor

GlaxoSmithKline — full company profile →

Who can join

Adults 18 to 60, any sex, with Diabetes Mellitus, Type 2. Healthy volunteers can join.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Safety and tolerability change from baseline in laboratory assessments
  Time frame: Part A: Approximately 58 days and Part B: Approximately 38 days.
  Hematology, Clinical Chemistry, Urinalysis
• Safety and tolerability change from baseline in electrocardiaogram (ECG) reading
  Time frame: Part A: Approximately 58 days and Part B: Approximately 38 days.
  12-lead ECG and continuous ECG monitoring.
• Safety and tolerability change from baseline in fluid intake
  Time frame: FPart A: Approximately 58 days and Part B: Approximately 38 days.
  urine output, and the number of micturations will be recorded.
• Safety and tolerability change from baseline in electrolytes
  Time frame: Part A: Approximately 58 days and Part B: Approximately 38 days.
  Blood electrolyte concentrations (Na, K, Cl, Ca, Mg and bicarbonate)
• Safety and Tolerability change from baseline in creatinine clearance
  Time frame: Part A: Approximately 58 days and Part B: Approximately 38 days.
  creatinine clearance (24-hours \[h\])
• Composite of pharmacokinetic parameters of GSK189075A, GSK189074A, and GSK279782A
  Time frame: Part A: up to 24 hours post dose for five periods. Part B: For 24 hours post dose for 3 periods. Collected at the following: pre-dose, and 10 min, 20 min, 30 min, 45 min, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, , 8, 12, 16 and 24h post-dose.
  Area under the plasma concentration-time curve \[AUC(0 last)\], Area under the plasma concentration-time curve \[AUC(0-infinity)\], Maximum observed plasma concentration (Cmax), Time to maximum observed plasma concentration (tmax), Plasma elimination half-life (t1/2), Area under the plasma concentration-time curve for the metabolite \[AUCm(0-last)\]/ Area under the plasma concentration-time curve

Sponsor's own description

This is a double blind, randomised, placebo controlled, single dose escalation, first-time-in-human, 5-way crossover study to assess the safety, tolerability, pharmacokinetic and pharmacodynamic parameters of ascending doses of GSK189075A in healthy subjects (Part A). Single doses will be given to 10 healthy subjects. The planned doses are 20mg, 50mg, 150mg, 500mg, and 1000mg. Each subject will receive 4 of the 5 active doses and a placebo separated by a washout of 5-10 days. A second cohort of 6 subjects with type 2 diabetes mellitus will receive 2 active doses and a placebo along with oral glucose in a three-way, randomised, placebo controlled, crossover design to assess glucose lowering following GSK189075A administration (Part B). Blood samples will be taken throughout the study day for pharmacokinetic analysis of prodrug and metabolites. Safety will be assessed by measurement of blood glucose, blood pressure, heart rate, ECGs, laboratory safety screens, and collection of adverse events.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. First human dose-escalation study with remogliflozin etabonate, a selective inhibitor of the sodium-glucose transporter 2 (SGLT2), in healthy subjects and in subjects with type 2 diabetes mellitus.
   Kapur A, O'Connor-Semmes R, Hussey EK, Dobbins RL, et al · · 2013 · cited 36× · PMID 23668634 · DOI 10.1186/2050-6511-14-26