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A Four-Part Study to Assess the Safety, Tolerability, PK and PD of ONO-5788 in Healthy Adult Volunteers

Primary Purpose

Acromegaly

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

ONO-5788

ONO-5788 Placebo

Octreotide

About this trial

This is an interventional treatment trial for Acromegaly

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

Celerion

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Active Comparator

Arm Label

ONO-5788 Part A1

ONO-5788 Placebo Part A1

ONO-5788 Part A2

ONO-5788 Placebo Part A2

ONO-5788 Part B

ONO-5788 Placebo Part B

ONO-5788 Part C

ONO-5788 Placebo Part C

ONO-5788 Part D

ONO-5788 Placebo Part D

Octreotide Part D

Arm Description

Single ascending doses of ONO-5788 or placebo in fasted healthy volunteers randomized 6 active : 2 placebo per group

Single dose (1-2 groups) of ONO-5788 or placebo in healthy volunteers under fed conditions randomized 6 active : 2 placebo per group

Multiple ascending doses of ONO-5788 or placebo in healthy volunteers randomized 8 active : 2 placebo per group

Single doses of ONO-5788 or placebo in elderly female or elderly male healthy volunteers randomized 6 active : 2 placebo per group

Single doses of ONO-5788, octreotide or placebo in healthy volunteers stimulated with growth hormone release hormone (GHRH) and arginine

Outcomes

Primary Outcome Measures

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.

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.

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.

Number of participants with ECG abnormalities

Number of participants with ECG abnormalities will be reported

Number of participants with clinical laboratory abnormalities

Number of participants with clinical laboratory abnormalities will be reported

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

Secondary Outcome Measures

Pharmacokinetics (AUC)

Assessment of the plasma area under the curve of ONO-5788 and metabolites (Parts A, B and C only)

Pharmacokinetics (AUC) - food effect

Effect of food on the plasma area under the curve of ONO-5788 and metabolites (Parts A only)

Pharmacokinetics (Cmax)

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

Effect of food on the maximum observed plasma concentration of ONO-5788, and metabolites (Part A only)

Pharmacokinetics (Tmax)

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

Effect of food on the time to reach Cmax for ONO-5788, metabolites (Part A only)

Pharmacokinetics (Ctrough)

Assessment of trough levels for ONO-5788 and metabolites immediately before dosing (Part B only)

Pharmacokinetics (T1/2)

Assessment of the elimination half-life of ONO-5788 and metabolites (Parts A, B and C only)

Pharmacokinetics (T1/2) - food effect

Effect of food on the elimination half-life of ONO-5788 and metabolites (metabolite) (Part A only)

Pharmacokinetics (CL/F)

Assessment of the apparent clearance rate of ONO-5788 (Parts A & C)

Pharmacokinetics (CL/F) - food effect

Effect of food on the apparent clearance rate of ONO-5788 (Part A only)

Pharmacokinetics (Cave)

Average concentration of ONO-5788/metabolites/Octreotide (Part D only)

Pharmacodynamics (IGF-1)

Assessment of the effects of ONO-5788 on IGF-1 levels (Part B only)

Pharmacodynamics (Growth Hormone)

Assessment of the effects of ONO-5788 on GH levels (Part B)

Pharmacodynamics (Growth Hormone)

Assessment of the effects of ONO-5788 on GHRH & arginine stimulated GH levels (Part D)

Pharmacodynamics (IGFBP3)

Assessment of the effects of ONO-5788 on IGFBP3 levels (Part B only)

Full Information

NCT ID

NCT03571594

First Posted

June 1, 2018

Last Updated

June 3, 2019

Sponsor

Ono Pharmaceutical Co. Ltd

1. Study Identification

Unique Protocol Identification Number

NCT03571594

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2019

Overall Recruitment Status

Terminated

Why Stopped

The study met a pre-defined protocol study stopping criteria

Study Start Date

June 7, 2018 (Actual)

Primary Completion Date

May 16, 2019 (Actual)

Study Completion Date

May 16, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Ono Pharmaceutical Co. Ltd

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acromegaly

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

Double-blind (Parts A, B &C). Open-label (Part D only)

Allocation

Randomized

Enrollment

76 (Actual)

8. Arms, Groups, and Interventions

Arm Title

ONO-5788 Part A1

Arm Type

Experimental

Arm Description

Single ascending doses of ONO-5788 or placebo in fasted healthy volunteers randomized 6 active : 2 placebo per group

Arm Title

ONO-5788 Placebo Part A1

Arm Type

Placebo Comparator

Arm Description

Single ascending doses of ONO-5788 or placebo in fasted healthy volunteers randomized 6 active : 2 placebo per group

Arm Title

ONO-5788 Part A2

Arm Type

Experimental

Arm Description

Single dose (1-2 groups) of ONO-5788 or placebo in healthy volunteers under fed conditions randomized 6 active : 2 placebo per group

Arm Title

ONO-5788 Placebo Part A2

Arm Type

Placebo Comparator

Arm Description

Single dose (1-2 groups) of ONO-5788 or placebo in healthy volunteers under fed conditions randomized 6 active : 2 placebo per group

Arm Title

ONO-5788 Part B

Arm Type

Experimental

Arm Description

Multiple ascending doses of ONO-5788 or placebo in healthy volunteers randomized 8 active : 2 placebo per group

Arm Title

ONO-5788 Placebo Part B

Arm Type

Placebo Comparator

Arm Description

Multiple ascending doses of ONO-5788 or placebo in healthy volunteers randomized 8 active : 2 placebo per group

Arm Title

ONO-5788 Part C

Arm Type

Experimental

Arm Description

Single doses of ONO-5788 or placebo in elderly female or elderly male healthy volunteers randomized 6 active : 2 placebo per group

Arm Title

ONO-5788 Placebo Part C

Arm Type

Placebo Comparator

Arm Description

Single doses of ONO-5788 or placebo in elderly female or elderly male healthy volunteers randomized 6 active : 2 placebo per group

Arm Title

ONO-5788 Part D

Arm Type

Experimental

Arm Description

Single doses of ONO-5788, octreotide or placebo in healthy volunteers stimulated with growth hormone release hormone (GHRH) and arginine

Arm Title

ONO-5788 Placebo Part D

Arm Type

Placebo Comparator

Arm Description

Single doses of ONO-5788, octreotide or placebo in healthy volunteers stimulated with growth hormone release hormone (GHRH) and arginine

Arm Title

Octreotide Part D

Arm Type

Active Comparator

Arm Description

Single doses of ONO-5788, octreotide or placebo in healthy volunteers stimulated with growth hormone release hormone (GHRH) and arginine

Intervention Type

Drug

Intervention Name(s)

ONO-5788

Intervention Description

Investigational drug

Intervention Type

Drug

Intervention Name(s)

ONO-5788 Placebo

Intervention Description

Placebo Comparator

Intervention Type

Drug

Intervention Name(s)

Octreotide

Other Intervention Name(s)

Sandostatin

Intervention Description

Active Comparator in Part D

Primary Outcome Measure Information:

Title

Number of participants with treatment emergent adverse events by severity

Description

An adverse event is any untoward medical occurrence in a participant who receive study drug without regard to possible causal relationship.

Time Frame