Brief Title
A Four-Part Study to Assess the Safety, Tolerability, PK and PD of ONO-5788 in Healthy Adult Volunteers
Official Title
A Randomized, Double-blind, Placebo-Controlled, Four- Part Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ONO-5788 in Healthy Adult Volunteers
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.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
Number of participants with treatment emergent adverse events by severity
Secondary Outcome
Pharmacokinetics (AUC)
Condition
Acromegaly
Intervention
ONO-5788
Study Arms / Comparison Groups
ONO-5788 Part A1
Description: Single ascending doses of ONO-5788 or placebo in fasted healthy volunteers randomized 6 active : 2 placebo per group
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
76
Start Date
June 7, 2018
Completion Date
May 16, 2019
Primary Completion Date
May 16, 2019
Eligibility Criteria
Inclusion Criteria:
- 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).
Exclusion Criteria:
- 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.
- History or presence of alcoholism or drug abuse within the past 2 years prior to the
first dosing.
- History or presence of hypersensitivity or idiosyncratic reaction to the study
drugs,excipients or related compounds.
- History or presence of:
1. Gallstones, cholangitis, and/or cholecystitis or clinically significant findings
on gallbladder ultrasound as determined by the Principal Investigator;
2. Pancreatitis;
3. Hypothyroidism;
4. Known diabetes mellitus type 1 or type 2;
5. Hypocalcaemia or hypokalemia;
6. Hypoglycemia or hyperglycemia or fasting blood glucose outside normal local
range;
7. Thrombocytopenia or other clinically significant hematologic abnormalities;
8. Inflammatory bowel disease, irritable bowel syndrome, or abdominal surgery;
9. Known vitamin B12 deficiency.
10. Abnormal gallbladder ejection fraction on hepatobiliary iminodiacetic acid (HIDA)
scan at screening (Part B only)
- Positive urine drug, alcohol or cotinine results at screening or check in.
- 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.
- Positive results at screening for human immunodeficiency virus (HIV), hepatitis B
surface antigen (HBsAg) or hepatitis C virus (HCV).
- 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.
- 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.
- Donation of blood or significant blood loss within 56 days prior to the first dosing.
- Plasma donation within 7 days prior to the first dosing.
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Contacts
Terry O'Reilly, MD, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT03571594
Organization ID
ONO-5788-01
Responsible Party
Sponsor
Study Sponsor
Ono Pharmaceutical Co. Ltd
Study Sponsor
Terry O'Reilly, MD, Principal Investigator, Celerion
Verification Date
June 2019