The purpose of this study is to assess the safety,tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of an extended dosing regimen of ITF2984: part A, designed as double-blind, placebo-controlled, randomized, tested an extended dosing regimen, i.e. 14 consecutive dosing days and higher doses, i.e. up to 6000 mcg/day and in part B, open label, continuous subcutaneous infusion for 7 days were tested as ascending doses of ITF2984 up to 9000 mcg/day of ITF2984.
This was a two part Phase I repeated incremental doses study in male healthy volunteers. The study was conducted in two parts. A total of 36 subjects was planned to be enrolled in Part A and 36 subjects in Part B. Part A was performed according to a double blind, randomized, placebo controlled design and included three sequential dose groups of repeat doses. Each group enrolled 12 subjects on ITF2984 or placebo (ratio 9 active: 3 placebo) and received ITF2984 s.c. or placebo twice daily for 14 days. For all three groups the last dose was planned to be the first dose on Day 14. The study started with the Group 1 2000mcg s.c. b.i.d., Group 2 received 3000mcg b.i.d. after an interim review of the safety and PK data of the 2000mcg dose level. Group 3 received 100mcg s.c. to gather data to complete the PK/PD profile of ITF2984. Subjects were screened up to 28 days before dosing with ITF2984/placebo that took place on Days 1-14. For all Groups, on day -1 and day 13 subjects received the exogenous tests administration (GHRH, Arginin and TRH) 30 minutes after the first morning administration of ITF2984/placebo. Part B was open label, and planned for six sequential dose groups of 6 subjects each. In each group subjects received ITF2984 continuous subcutaneous infusion for 7 consecutive days. The dose was escalated, from the starting dose of 900 mcg, by a maximum of three fold or more cautiously, if deemed necessary. The decision to test higher dose levels was based on review of safety and PK data from the previous dose level(s). After a 28 day screening period, subjects were admitted to the clinical unit on the evening of day -2. ITF2984 continuous infusion planned from day 1 to day 8 in the morning. On day -1 (the day prior to the start of infusion) subjects received the exogenous/challenge test administrations (GH-RH+Arginina and TRH). On day 7 the challenge tests were repeated.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
36
Centro Ricerche Cliniche
Verona, Verona, Italy
To investigate the safety profile of repeated doses of ITF2984
Adverse events; 12-lead ECG, including QTc; vital signs (blood pressure, heart rate and body temperature); clinical laboratory evaluations (haematology, clinical chemistry including peripheral glucose, urinalysis), gallbladder volume evaluation.
Time frame: 15 days
To investigate the pharmacokinetics (PK) profile of multiple ascending doses of ITF2984
Plasma concentrations of ITF2984
Time frame: 15 days and day 8
To investigate the safety profile of repeated doses of ITF2984
Adverse events; 12-lead ECG, including QTc; vital signs (blood pressure, heart rate and body temperature); clinical laboratory evaluations (haematology, clinical chemistry including peripheral glucose, urinalysis.
Time frame: 8 days
To investigate the effects of ITF2984 on growth hormone (GH) after exogenous growth hormone releasing hormone (GH-RH) and arginine stimulus
PD biomarkers of GH
Time frame: 13 Days and 7 Days
To investigate the effects of ITF2984 on thyroid stimulating hormone (TSH) after exogenous thyrotrophin releasing hormone (TRH) stimulus
PD biomarkers of TSH
Time frame: 13 days and 7 days
To investigate the effects of ITF2984 on IGF-1
PD biomarkers of IGF-1
Time frame: 13 days and 7 days
To investigate the effects of ITF2984 on glucose
PD biomarkers of glucose
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Time frame: 14 days and 6 days
To investigate the effects of ITF2984 on prolactin (PRL) after exogenous thyrotrophin releasing hormone (TRH) stimulus
PD biomarkers of PRL
Time frame: 13 days and 7 days
To investigate the effects of ITF2984 on insulin
PD biomarkers of insulin
Time frame: 14 days and 6 days
To investigate the effects of ITF2984 on glucagon
PD biomarkers of glucagon
Time frame: 14 days and 6 days