A Phase 1, first in human, three-part, single centre study to assess the safety, tolerability, PK and PD of single ascending subcutaneous doses of HTL0030310 in healthy subjects
This is a first in human, three part study with the objective to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of single ascending subcutaneous doses of HTL0030310 in healthy subjects. Part 1 is a double-blind, placebo-controlled, randomised study assessing single ascending doses of HTL0030310. Part 2 is a site-blind (sponsor unblinded), placebo-controlled, part-randomised, fixed-sequence, single-dose, 4-period study assessing the PD of a positive control, pasireotide, following administration of challenge agents. Part 3 is a double-blind, placebo-controlled, part-randomised, fixed-sequence, single-dose, HTL0030310 proof of pharmacological effect study, where PD effects of HTL0030310 will be investigated following administration of challenge agents. The challenge agents administered in this study will be: oral glucose tolerance test (OGTT), Growth hormone-releasing hormone (GHRH), and corticotrophin releasing hormone (CRH) combined with desmopressin.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
42
Solution for Subcutaneous injection
Pasireotide 600 μg for subcutaneous injection
Matching placebo Solution
Quotient Sciences
Nottingham, United Kingdom
Part 1: Number of treatment related adverse events (as determined by abnormal clinical laboratory tests, vitals signs, ECG parameters, Holter ECG parameters and injection site reactions)
Safety and Tolerability
Time frame: Admission up to 8 days post dose
Part 2 and Part 3 Area under the effect time curve (EAUC) 1) for insulin, glucose, glucagon, GLP1, C-peptide and GIP level 2) for GH 3) ACTH and cortisol
Pharmacodynamics
Time frame: Predose up to 4 hours post dose
Part 2 and Part 3 Maximum observed effect (EMax) 1) for insulin, glucose, glucagon, GLP1, C-peptide and GIP level 2) for GH 3) ACTH and cortisol
Pharmacodynamics
Time frame: Predose up to 4 hours post dose
Part 2 and Part 3 Time to reach Maximum observed effect (TEMax) 1) for insulin, glucose, glucagon, GLP1, C-peptide and GIP level 2) for GH 3) ACTH and cortisol
Pharmacodynamics
Time frame: Predose up to 4 hours post dose
Part 1 Maximum observed plasma concentration (Cmax) of single subcutaneous doses of HTL0030310
Pharmacokinetics
Time frame: Pre dose to 144 hours post dose
Part 1 Time to reach Maximum observed plasma concentration (Tmax) of single subcutaneous doses of HTL0030310
Pharmacokinetics
Time frame: Pre dose to 144 hours post dose
Part 1 Area under the curve (AUC) of single subcutaneous doses of HTL0030310
Pharmacokinetics
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Time frame: Pre dose to 144 hours post dose
Part 2 Maximum observed plasma concentration (Cmax) of single subcutaneous doses of pasireotide
Pharmacokinetics
Time frame: Predose to 24 hours postdose
Part 2 Time to reach Maximum observed plasma concentration (Tmax) of single subcutaneous doses of pasireotide
Pharmacokinetics
Time frame: Predose to 24 hours postdose
Part 2 Area under the curve (AUC) of single subcutaneous doses of pasireotide
Pharmacokinetics
Time frame: Predose to 24 hours postdose
Part 3: Number of treatment related adverse events (as determined by abnormal clinical laboratory tests, vitals signs, ECG parameters and injection site reactions)
Safety and Tolerability
Time frame: Admission up to 8 to 10 days post final dose
Part 3 Maximum observed plasma concentration (Cmax) of single subcutaneous doses of HTL0030310
Pharmacokinetics
Time frame: Predose to 96 hours postdose
Part 3 Time to reach Maximum observed plasma concentration (Tmax) of single subcutaneous doses of HTL0030310
Pharmacokinetics
Time frame: Predose to 96 hours postdose
Part 3 Area under the curve (AUC) of single subcutaneous doses of HTL0030310
Pharmacokinetics
Time frame: Predose to 96 hours postdose