This is a first in human study to determine the safety, tolerability, pharmacokinetics and pharmacodynamics of ONO-5788 in healthy adult volunteers. This study will be conducted in 4 parts: a single-ascending dose part, a multiple-ascending dose part, an elderly part and a proof of principle part.
This single centre study will be comprised of 4 parts, Part A (SAD; up to 7 cohorts, 8 subjects per cohort and including an assessment of food effect), a multiple-dose part (up to 4 doses, 10 subjects per cohort); an elderly cohort (8 subjects per gender) and a proof of principle part. The single ascending dose part (Part A) comprises of increasing doses of an oral solution or capsule, with an investigation of the potential for food effects. The multiple ascending dose part (Part B, MAD; 14 days dosing) will be initiated after the PK and safety data are available from the single ascending dose part. Subjects in Part B will have ultrasound scans of the gallbladder during the study and at screening a HIDA scan will be performed. An evaluation of the PK in the elderly and any potential gender differences will also be evaluated in Part C. Subjects in Part C will have an ultrasound of the gallbladder at screening. Part D will be a proof of principle evaluation where the effects of ONO-5788 to inhibit the GHRH and arginine-stimulated GH release will be evaluated. Octreotide acetate is a reference arm in this part of the study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
76
Investigational drug
Placebo Comparator
Active Comparator in Part D
Celerion
Tempe, Arizona, United States
Number of participants with treatment emergent adverse events by severity
An adverse event is any untoward medical occurrence in a participant who receive study drug without regard to possible causal relationship.
Time frame: Part A - up to day 8; Part B - at least day 21; Part C - at least day 21; and Part D - up to day 28
Number of participants with serious adverse events (SAEs)
An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death, initial or prolonged hospitalization, life-threatening experience or persistent disability.
Time frame: Part A - up to day 8; Part B - at least day 21; Part C - at least day 21; and Part D - up to day 28
Number of participants with clinically significant changes in vital signs
Number of participants with clinically significant changes in vital signs including pulse/heart rate, respiratory rate, and blood pressure will be reported.
Time frame: Part A - up to day 8; Part B - at least day 21; Part C - at least day 21; and Part D - up to day 28
Number of participants with ECG abnormalities
Number of participants with ECG abnormalities will be reported
Time frame: Part A - up to day 8; Part B - at least day 21; Part C - at least day 21; and Part D - up to day 28
Number of participants with clinical laboratory abnormalities
Number of participants with clinical laboratory abnormalities will be reported
Time frame: Part A - up to day 8; Part B - at least day 21; Part C - at least day 21; and Part D - up to day 28
Number of participants with clinically significant change in ultrasound of gallbladder
Number of participants with clinically significant change in ultrasound of gallbladder will be reported
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time frame: Part B - up to day 21
Pharmacokinetics (AUC)
Assessment of the plasma area under the curve of ONO-5788 and metabolites (Parts A, B and C only)
Time frame: Day 1 through Day 14
Pharmacokinetics (AUC) - food effect
Effect of food on the plasma area under the curve of ONO-5788 and metabolites (Parts A only)
Time frame: Day 1
Pharmacokinetics (Cmax)
Assessment of the maximum observed plasma concentration of ONO-5788, metabolites (Parts A, B, C \& D) and octreotide (Part D only)
Time frame: Day 1 through Day 14
Pharmacokinetics (Cmax) - food effect
Effect of food on the maximum observed plasma concentration of ONO-5788, and metabolites (Part A only)
Time frame: Day 1
Pharmacokinetics (Tmax)
Assessment of the time to reach Cmax for ONO-5788, metabolites (Parts A, B, C \& D) and octreotide (Part D only)
Time frame: Day 1 through Day 14
Pharmacokinetics (Tmax) - food effect
Effect of food on the time to reach Cmax for ONO-5788, metabolites (Part A only)
Time frame: Day 1 through Day 14
Pharmacokinetics (Ctrough)
Assessment of trough levels for ONO-5788 and metabolites immediately before dosing (Part B only)
Time frame: Day 1 through Day 14
Pharmacokinetics (T1/2)
Assessment of the elimination half-life of ONO-5788 and metabolites (Parts A, B and C only)
Time frame: Day 1 through Day 14
Pharmacokinetics (T1/2) - food effect
Effect of food on the elimination half-life of ONO-5788 and metabolites (metabolite) (Part A only)
Time frame: Day 1
Pharmacokinetics (CL/F)
Assessment of the apparent clearance rate of ONO-5788 (Parts A \& C)
Time frame: Day 1
Pharmacokinetics (CL/F) - food effect
Effect of food on the apparent clearance rate of ONO-5788 (Part A only)
Time frame: Day 1
Pharmacokinetics (Cave)
Average concentration of ONO-5788/metabolites/Octreotide (Part D only)
Time frame: Day 1
Pharmacodynamics (IGF-1)
Assessment of the effects of ONO-5788 on IGF-1 levels (Part B only)
Time frame: Day 1 through Day 21
Pharmacodynamics (Growth Hormone)
Assessment of the effects of ONO-5788 on GH levels (Part B)
Time frame: Day 1 through Day 21
Pharmacodynamics (Growth Hormone)
Assessment of the effects of ONO-5788 on GHRH \& arginine stimulated GH levels (Part D)
Time frame: Day 1
Pharmacodynamics (IGFBP3)
Assessment of the effects of ONO-5788 on IGFBP3 levels (Part B only)
Time frame: Day 1 through Day 21