Clinical trial NCT03571594: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Acromegaly
Lead sponsor: Ono Pharmaceutical Co. Ltd
Sponsor class: INDUSTRY
First posted: 2018-06-27
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Number of participants with treatment emergent adverse events by severity
timeFrame: 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
measure: Number of participants with serious adverse events (SAEs)
timeFrame: 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
measure: Number of participants with clinically significant changes in vital signs
timeFrame: 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
measure: Number of participants with ECG abnormalities
timeFrame: 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
measure: Number of participants with clinical laboratory abnormalities
timeFrame: 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
measure: Number of participants with clinically significant change in ultrasound of gallbladder
timeFrame: Part B - up to day 21
Secondary outcomes:
measure: Pharmacokinetics (AUC)
timeFrame: Day 1 through Day 14
measure: Pharmacokinetics (AUC) - food effect
timeFrame: Day 1
measure: Pharmacokinetics (Cmax)
timeFrame: Day 1 through Day 14
measure: Pharmacokinetics (Cmax) - food effect
timeFrame: Day 1
measure: Pharmacokinetics (Tmax)
timeFrame: Day 1 through Day 14
measure: Pharmacokinetics (Tmax) - food effect
timeFrame: Day 1 through Day 14
measure: Pharmacokinetics (Ctrough)
timeFrame: Day 1 through Day 14
measure: Pharmacokinetics (T1/2)
timeFrame: Day 1 through Day 14
measure: Pharmacokinetics (T1/2) - food effect
timeFrame: Day 1
measure: Pharmacokinetics (CL/F)
timeFrame: Day 1
measure: Pharmacokinetics (CL/F) - food effect
timeFrame: Day 1
measure: Pharmacokinetics (Cave)
timeFrame: Day 1
measure: Pharmacodynamics (IGF-1)
timeFrame: Day 1 through Day 21
measure: Pharmacodynamics (Growth Hormone)
timeFrame: Day 1 through Day 21
measure: Pharmacodynamics (Growth Hormone)
timeFrame: Day 1
measure: Pharmacodynamics (IGFBP3)
timeFrame: Day 1 through Day 21
Other outcomes:
Locations:
city: Tempe
country: United States
facility: Celerion
state: Arizona
Study officials:
affiliation: Celerion
name: Terry O'Reilly, MD
role: PRINCIPAL_INVESTIGATOR
References: