A Four-Part Study to Assess the Safety, Tolerability, PK and PD of ONO-5788 in Healthy Adult Volunteers
- Conditions
- Acromegaly
- Interventions
- Registration Number
- NCT03571594
- Lead Sponsor
- Ono Pharmaceutical Co. Ltd
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 76
- Healthy, adult, male and female (women of non-child bearing potential, surgically sterile) volunteers, 18-55 years of age, inclusive, at screening (Parts A & B only).
- Healthy, adult, males and female (women of non-child bearing potential), ≥65 years of age at screening (Part C only).
- Healthy, adult, male, 18-40 years of age, inclusive, at screening (Part D only).
- Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs or ECG abnormalities (All Parts).
- Body mass index (BMI) of ≥18.5 to ≤30 kg/m2 at screening (Parts A, B & C).
- Body mass index (BMI) of ≥18.5 to <25 kg/m2 at screening (Part D only).
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History of any illness that, in the opinion of the PI or designee, might confound the results of the study or poses an additional risk to the subject by their participation in the study.
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History or presence of alcoholism or drug abuse within the past 2 years prior to the first dosing.
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History or presence of hypersensitivity or idiosyncratic reaction to the study drugs,excipients or related compounds.
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History or presence of:
- Gallstones, cholangitis, and/or cholecystitis or clinically significant findings on gallbladder ultrasound as determined by the Principal Investigator;
- Pancreatitis;
- Hypothyroidism;
- Known diabetes mellitus type 1 or type 2;
- Hypocalcaemia or hypokalemia;
- Hypoglycemia or hyperglycemia or fasting blood glucose outside normal local range;
- Thrombocytopenia or other clinically significant hematologic abnormalities;
- Inflammatory bowel disease, irritable bowel syndrome, or abdominal surgery;
- Known vitamin B12 deficiency.
- Abnormal gallbladder ejection fraction on hepatobiliary iminodiacetic acid (HIDA) scan at screening (Part B only)
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Positive urine drug, alcohol or cotinine results at screening or check in.
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Clinically significant serum electrolyte (sodium, potassium, chloride, bicarbonate) abnormalities at screening or each check-in, in the estimation and clinical judgment of the PI or designee.
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Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV).
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Seated blood pressure is less than 90/40 millimeter of mercury (mmHg) or greater than 140/90 mmHg (160/95 mmHg for Part C) at screening.
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Has engaged in strenuous physical exercise in the 48 hours prior first dosing or intends to undergo strenuous physical exercise at any time throughout the study.
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Donation of blood or significant blood loss within 56 days prior to the first dosing.
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Plasma donation within 7 days prior to the first dosing.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description ONO-5788 Part A2 ONO-5788 Single dose (1-2 groups) of ONO-5788 or placebo in healthy volunteers under fed conditions randomized 6 active : 2 placebo per group ONO-5788 Placebo Part A2 ONO-5788 Placebo Single dose (1-2 groups) of ONO-5788 or placebo in healthy volunteers under fed conditions randomized 6 active : 2 placebo per group ONO-5788 Part B ONO-5788 Multiple ascending doses of ONO-5788 or placebo in healthy volunteers randomized 8 active : 2 placebo per group ONO-5788 Part D ONO-5788 Single doses of ONO-5788, octreotide or placebo in healthy volunteers stimulated with growth hormone release hormone (GHRH) and arginine ONO-5788 Placebo Part B ONO-5788 Placebo Multiple ascending doses of ONO-5788 or placebo in healthy volunteers randomized 8 active : 2 placebo per group ONO-5788 Placebo Part A1 ONO-5788 Placebo Single ascending doses of ONO-5788 or placebo in fasted healthy volunteers randomized 6 active : 2 placebo per group ONO-5788 Part C ONO-5788 Single doses of ONO-5788 or placebo in elderly female or elderly male healthy volunteers randomized 6 active : 2 placebo per group ONO-5788 Placebo Part C ONO-5788 Placebo Single doses of ONO-5788 or placebo in elderly female or elderly male healthy volunteers randomized 6 active : 2 placebo per group ONO-5788 Placebo Part D ONO-5788 Placebo Single doses of ONO-5788, octreotide or placebo in healthy volunteers stimulated with growth hormone release hormone (GHRH) and arginine ONO-5788 Part A1 ONO-5788 Single ascending doses of ONO-5788 or placebo in fasted healthy volunteers randomized 6 active : 2 placebo per group Octreotide Part D Octreotide Single doses of ONO-5788, octreotide or placebo in healthy volunteers stimulated with growth hormone release hormone (GHRH) and arginine
- Primary Outcome Measures
Name Time Method Number of participants with treatment emergent adverse events by severity 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 An adverse event is any untoward medical occurrence in a participant who receive study drug without regard to possible causal relationship.
Number of participants with ECG abnormalities 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 will be reported
Number of participants with clinical laboratory abnormalities 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 will be reported
Number of participants with clinically significant change in ultrasound of gallbladder Part B - up to day 21 Number of participants with clinically significant change in ultrasound of gallbladder will be reported
Number of participants with serious adverse events (SAEs) 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 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.
Number of participants with clinically significant changes in vital signs 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 including pulse/heart rate, respiratory rate, and blood pressure will be reported.
- Secondary Outcome Measures
Name Time Method Pharmacokinetics (AUC) Day 1 through Day 14 Assessment of the plasma area under the curve of ONO-5788 and metabolites (Parts A, B and C only)
Pharmacokinetics (T1/2) Day 1 through Day 14 Assessment of the elimination half-life of ONO-5788 and metabolites (Parts A, B and C only)
Pharmacodynamics (IGF-1) Day 1 through Day 21 Assessment of the effects of ONO-5788 on IGF-1 levels (Part B only)
Pharmacodynamics (IGFBP3) Day 1 through Day 21 Assessment of the effects of ONO-5788 on IGFBP3 levels (Part B only)
Pharmacokinetics (AUC) - food effect Day 1 Effect of food on the plasma area under the curve of ONO-5788 and metabolites (Parts A only)
Pharmacokinetics (Cmax) Day 1 through Day 14 Assessment of the maximum observed plasma concentration of ONO-5788, metabolites (Parts A, B, C \& D) and octreotide (Part D only)
Pharmacokinetics (Cmax) - food effect Day 1 Effect of food on the maximum observed plasma concentration of ONO-5788, and metabolites (Part A only)
Pharmacokinetics (Ctrough) Day 1 through Day 14 Assessment of trough levels for ONO-5788 and metabolites immediately before dosing (Part B only)
Pharmacokinetics (Cave) Day 1 Average concentration of ONO-5788/metabolites/Octreotide (Part D only)
Pharmacokinetics (Tmax) Day 1 through Day 14 Assessment of the time to reach Cmax for ONO-5788, metabolites (Parts A, B, C \& D) and octreotide (Part D only)
Pharmacokinetics (Tmax) - food effect Day 1 through Day 14 Effect of food on the time to reach Cmax for ONO-5788, metabolites (Part A only)
Pharmacokinetics (CL/F) Day 1 Assessment of the apparent clearance rate of ONO-5788 (Parts A \& C)
Pharmacodynamics (Growth Hormone) Day 1 Assessment of the effects of ONO-5788 on GHRH \& arginine stimulated GH levels (Part D)
Pharmacokinetics (T1/2) - food effect Day 1 Effect of food on the elimination half-life of ONO-5788 and metabolites (metabolite) (Part A only)
Pharmacokinetics (CL/F) - food effect Day 1 Effect of food on the apparent clearance rate of ONO-5788 (Part A only)
Trial Locations
- Locations (1)
Celerion
🇺🇸Tempe, Arizona, United States