This is a two-part, single centre, double-blind (within cohorts), randomised, placebo-controlled, single (Part 1) and multiple (Part 2) ascending subcutaneous dose study in lean to overweight or obese but otherwise healthy men (Part 1) and men and non-pregnant, non-lactating women (Part 2). The primary objective is to assess the safety and tolerability. Secondary objectives are to characterize the pharmacokinetics (PK) and to investigate pharmacodynamic effects.
This is a phase 1 clinical trial of a new long-acting amylin analogue GUB014295 in two parts. Trial design: Part 1 is a double-blind (within cohorts), randomised, placebo-controlled, single ascending dose (SAD) study. It is planned to enrol 4 cohorts of 8 subjects (Regimens A, B, C and D), with 2 additional optional cohorts of 8 subjects (Regimens E and F). Part 2A is a double-blind (within cohorts), randomised, placebo-controlled, multiple ascending dose (MAD) study. It is planned to enrol 2 cohorts of 8 subjects (Regimens G and H). Part 2B is a double-blind (within cohorts), randomised, placebo-controlled, MAD study. It is planned to enrol 3 cohorts of 12 subjects (Regimens I, J and K). Part 2C is a double-blind (within cohorts), randomised, placebo-controlled, MAD study. It is planned to enrol 2 cohorts of up to 12 subjects (Regimens L and M). The primary objective is to assess the safety and tolerability of a new long-acting amylin-analogue GUB014295. Secondary objectives are to characterize the pharmacokinetics (PK) of the long-acting amylin-analogue GUB014295 and to investigate if the long-acting amylin-analogue GUB014295 has possible pharmacodynamic effects measured as weight changes and changes in gastric emptying (paracetamol concentration) and changes in glucose, insulin, C-peptide, and glucagon during a mixed meal test.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
76
GUB014295 is a long-acting amylin analogue in development, a single subcutaneous dose is administered in part 1, multiple doses administered in part 2 of the study
GUB014295-PLACEBO is matching GUB014295 in appearance, a single subcutaneous dose is administered in part 1, multiple doses administered in part 2 of the study
Quotient Sciences
Nottingham, United Kingdom
Safety - Adverse Events (AE) incidence
To provide safety information for GUB014295 by assessing: incidence of AEs categorized in System Organ Class (SOC) according to MedDRA (and evaluating severity and duration for SOC). No formal hypothesis will be tested in the study. Descriptive summaries for all safety safety data for all placebo, each active treatment and all active will be provided (including changes from baseline)
Time frame: from baseline (day 0) to end of trial (day 29) part 1, (day 64) part 2A, (day 120) part 2B and (day 127) in Part 2C
Safety - changes in vital signs
To provide safety information for GUB014295 by assessing: Any changes from baseline for vital signs including: Blood pressure, Pulse/heart rate, oral temperature and respiratory frequency summarized as a ratio (baseline/end of trial). No formal hypothesis will be tested in the study. Descriptive summaries (as a relative change (ratio: 0 - 1) from day 0 to end of trial) for all safety safety data for all placebo, each active treatment and all active will be provided.
Time frame: from baseline (day 0) to end of trial (day 29) part 1, (day 64) part 2A, (day 120) part 2B and (day 127) in Part 2C
Safety - Safety laboratory parameters
To provide safety information for GUB014295 by assessing a wide range of laboratory parameters within hematology, coagulation, clinical chemistry, virology, urinalysis. No formal hypothesis will be tested in the study. Descriptive summaries (as a relative change (ratio: 0 - 1) from day 0 to day end of trial)) for all safety safety data for all placebo, each active treatment and all active will be provided.
Time frame: From baseline (day 0) to end of trial (day 29) part 1, (day 64) part 2A, (day 120) part 2B and (day 127) in Part 2C
Pharmacokinetic (PK) - Tmax and Cmax
PK parameters: Tmax, (time of observed maximum concentration), Cmax (maximum observed concentration), for GUB014295.
Time frame: from dosing (day 0) until maximum concentration after final dose
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Pharmacokinetic (PK) - area under the concentration curve (AUC)
PK parameters: AUC(0-72) area under the curve for the GUB014295 measured from dosing, until 72 hours post dose, AUC(0-168) area under the curve for the GUB014295 measured from dosing, until 168 hours post dose, AUC(0-last) area under the curve for the GUB014295 measured from dosing, until the time of last measurable concentration, AUC(0-inf) area under the curve for the GUB014295 concentration from dosing, extrapolated until infinity.
Time frame: From dosing (day 0) until end of trial (day 29) part 1, (day 64) part 2A, (day 120) part 2B and (day 127) in Part 2C
Pharmacokinetic (PK) - T1/2
PK parameters: T1/2: Terminal elimination half-life,
Time frame: from dosing (day 0) until end of trial (day 29)part 1, (day 64) part 2A, (day 120) part 2B and (day 127) in Part 2C
Pharmacokinetic (PK) - CL/F
PK parameters: CL/F: Total body clearance (CL) calculated after single subcutaneous administration where F (fraction of bioavailability) is unknown,
Time frame: from dosing (day 0) until end of trial (day 29) part 1, (day 64) part 2A, (day 120) part 2B and (day 127) in Part 2C
Pharmacokinetic (PK) - Vz/F
PK parameters: Vz/F: apparent volume of distribution (Vz) based on terminal phase calculated using AUC(0-inf) after a single subcutaneous administration where F (fraction of bioavailability) is unknown,
Time frame: From dosing (day 0) until end of trial (day 29) part 1, (day 64) part 2A, (day 120) part 2B and (day 127) in Part 2C