A Study of Treprostinil and a New Formulation of LY900014 in Healthy Japanese Participants

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02770521
• Collaborator: (none)
• Enrollment: 23
• Location: 1
• Arms: 4
• Duration (Months): 2
• Patients Per Site Per Month: 11.5

Study Details

Study Description

Brief Summary

The aims of this study are to evaluate:

• The safety and tolerability of a single dose of treprostinil given subcutaneously (as an injection just under the skin)

• The pharmacokinetic profile (how the body absorbs, breaks down, and gets rid of) of a single subcutaneous dose of a new LY900014 formulation in healthy Japanese participants.

The study has two parts. Participants may only enroll in one part.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Treprostinil; Drug: Placebo; Drug: LY900014; Drug: Insulin Lispro	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 23 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Basic Science
• Official Title: A Study to Evaluate the Safety and Tolerability of Subcutaneous Treprostinil and Pharmacokinetics of a Novel LY900014 Formulation in Healthy Japanese Subjects
• Study Start Date: May 1, 2016
• Actual Primary Completion Date: Jul 1, 2016
• Actual Study Completion Date: Jul 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treprostinil (Part A) Treprostinil administered as a single subcutaneous (SC) bolus injection.	Drug: Treprostinil; Administered SC.
Placebo Comparator: Placebo (Part A) Placebo administered as a single SC bolus injection.	Drug: Placebo; Administered SC.
Experimental: LY900014 (Part B) LY900014 (test) administered as a single SC bolus injection.	Drug: LY900014; Administered SC.; Other Names: Ultra-Rapid Lispro
Active Comparator: Insulin Lispro (Part B) Insulin lispro (reference) administered as a single SC bolus injection.	Drug: Insulin Lispro; Administered SC.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration [Part A: Baseline through Study Completion (up to 14 Days after Last Dose)]

   A summary of SAEs and other non-serious adverse events (AEs), regardless of causality, are reported in the Adverse Events module.

2. Pharmacokinetics (PK): Insulin Lispro Maximum Concentration (Cmax) (Part B) [Predose, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 90, 120, 150, 180, 240, 300, 360, and 420 Minutes Postdose]

   PK: Insulin Lispro Cmax (Part B)

3. PK: Insulin Lispro Area Under the Concentration-Time Curve From Time Zero to 30 Minutes (AUC[0-30min]) (Part B) [Predose, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 90, 120, 150, 180, 240, 300, 360, and 420 Minutes Postdose]

   PK: Insulin Lispro AUC(0-30min) (Part B)

Secondary Outcome Measures

1. PK: Treprostinil Time to Maximum Concentration (Tmax) (Part A) [15, 30, 60 and 120 Minutes Postdose]

   PK: Treprostinil Tmax (Part A)

2. PK: Maximum Concentration (Cmax) of Treprostinil (Part A) [15, 30, 60 and 120 Minutes Postdose]

   PK: Cmax of Treprostinil (Part A)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Overtly healthy Japanese

• Body mass index (BMI) 18.5 - 25 kilograms per square meter (kg/m²)

• Fasting plasma glucose ≥71 milligrams per deciliter (mg/dL) (3.9 millimoles per liter [mmol/L]) and <108 mg/dL (6.0 mmol/L) (Part B only)

• Have normal blood pressure, pulse rate, electrocardiogram (ECG), blood and urine laboratory test results that are acceptable for the study

Exclusion Criteria:

• Are currently enrolled in a clinical trial involving an investigational product or any other type of medical research judged not to be scientifically or medically compatible with this study

• Have participated in a clinical trial involving an investigational product within the 30 days before study entry.

• Have previously completed or withdrawn from this study or any other study investigating treprostinil or LY900014, and have previously received the investigational product

• Have or used to have health problems or laboratory test results or ECG readings that, in the opinion of the doctor, could make it unsafe to participate, or could interfere with understanding the results of the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Fukuoka		Japan	812-0025

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT02770521
• Other Study ID Numbers: 16071; I8B-JE-ITRK
• First Posted: May 12, 2016
• Last Update Posted: Jun 4, 2020
• Last Verified: Jul 1, 2016

• Additional relevant MeSH terms: Insulin Lispro; Treprostinil

Study Results

Participant Flow

Recruitment Details	This study had two parts: Part A was a two-period crossover. Part B was a three-period crossover with dose escalation. Healthy Japanese participants were eligible to enroll in one part. One randomized participant discontinued prior to study completion and was replaced. The replacement adopted the original participant's randomization scheme.

Arm/Group Title	Placebo/Treprostinil (Part A)	Treprostinil/Placebo (Part A)	15 U Insulin Lispro/15 U LY900014/30 U LY900014 (Part B)	7.5 U LY900014/15 U Insulin Lispro/30 U LY900014 (Part B)	7.5 U LY900014/15 U LY900014/15 U Insulin Lispro (Part B)	7.5 U LY900014/15 U LY900014/30 U LY900014 (Part B)
Arm/Group Description	Placebo given subcutaneously (SC) once in first study period. 1,000 nanograms (ng) of treprostinil given SC once in second study period. There was a minimum three day washout between doses.	1,000 ng of treprostinil given SC once in first study period. Matching placebo given SC once in second study period. There was a minimum three day washout between doses.	15 units (U) insulin lispro given SC once in first study period. 15 U LY900014 given SC once in second study period. 30 U LY900014 given SC once in third study period. There was a minimum three day washout between doses.	7.5 U LY900014 given SC once in first study period. 15 U insulin lispro given SC once in second study period. 30 U LY900014 given SC once in third study period. There was a minimum three day washout between doses.	7.5 U LY900014 given SC once in first study period. 15 U LY900014 given SC once in second study period. 15 U insulin lispro given SC once in third study period. There was a minimum three day washout between doses.	7.5 U LY900014 given SC once in first study period. 15 U LY900014 given SC once in second study period. 30 U LY900014 given SC once in third study period. There was a minimum three day washout between doses.
Period Title: Period One
STARTED	4	4	2	2	2	9
Received Study Drug	4	4	2	2	2	9
COMPLETED	4	4	2	2	2	9
NOT COMPLETED	0	0	0	0	0	0
Period Title: Period One
STARTED	4	4	2	2	2	9
Received Study Drug	4	4	2	2	2	9
COMPLETED	4	4	2	2	2	9
NOT COMPLETED	0	0	0	0	0	0
Period Title: Period One
STARTED	0	0	2	2	2	9
Received Study Drug	0	0	2	2	2	9
COMPLETED	0	0	2	2	2	9
NOT COMPLETED	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Treprostinil or Placebo (Part A)	LY900014 or Insulin Lispro (Part B)	Total
Arm/Group Description	Participants received either 1000 ng of treprostinil or matching placebo as a SC injection once in each of two study periods.	Participants received each of three doses of LY900014 (7.5 U, 15 U, 30 U) or 15 U of insulin lispro as a SC injection once in each of three study periods.	Total of all reporting groups
Overall Participants	8	15	23
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	26.3 (4.4)	26.1 (5.4)	26.2 (5.0)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	8 100%	15 100%	23 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	8 100%	15 100%	23 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	8 100%	15 100%	23 100%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
Japan	8 100%	15 100%	23 100%
Body Mass Index (BMI) (kilograms per meter squared (kg/m²)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms per meter squared (kg/m²)]	22.57 (2.00)	21.93 (2.19)	22.15 (2.10)

Outcome Measures

1. Primary Outcome

Title	Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
Description	A summary of SAEs and other non-serious adverse events (AEs), regardless of causality, are reported in the Adverse Events module.
Time Frame	Part A: Baseline through Study Completion (up to 14 Days after Last Dose)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug.

Arm/Group Title	Placebo (Part A)	Treprostinil (Part A)	15 U Insulin Lispro (Part B)	7.5 U LY900014 (Part B)	15 U LY900014 (Part B)	30 U LY900014 (Part B)
Arm/Group Description	Placebo given subcutaneously (SC) once in one of two study periods. There was a minimum three day washout between doses.	1,000 ng of treprostinil given SC once in one of two study periods. There was a minimum three day washout between doses.	15 units (U) insulin lispro given SC once in up to one of three study periods. There was a minimum three day washout between doses.	7.5 U LY900014 given SC once in up to one of three study periods. There was a minimum three day washout between doses.	15 U LY900014 given SC once in up to one of three study periods. There was a minimum three day washout between doses.	30 ULY900014 given SC once in up to one of three study periods. There was a minimum three day washout between doses.
Measure Participants	8	8	6	13	13	13
Number [participants]	0 0%	0 0%	0 0%	0 NaN	0 NaN	0 NaN

2. Primary Outcome

Title	Pharmacokinetics (PK): Insulin Lispro Maximum Concentration (Cmax) (Part B)
Description	PK: Insulin Lispro Cmax (Part B)
Time Frame	Predose, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 90, 120, 150, 180, 240, 300, 360, and 420 Minutes Postdose

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug LY900014 in Part B and had evaluable pharmacokinetic data. Per protocol, PK in Part B was not analyzed for 15 U Insulin Lispro (Humalog). This arm was included for only safety analysis.

Arm/Group Title	7.5 U LY900014 (Part B)	15 U LY900014 (Part B)	30 U LY900014 (Part B)
Arm/Group Description	7.5 U LY900014 given SC once in up to one of three study periods. There was a minimum three day washout between doses.	15 U LY900014 given SC once in up to one of three study periods. There was a minimum three day washout between doses.	30 U LY900014 given SC once in up to one of three study periods. There was a minimum three day washout between doses.
Measure Participants	13	13	13
Geometric Mean (Geometric Coefficient of Variation) [picomoles/liter (pmol/L)]	582 (42)	956 (41)	2170 (30)

3. Primary Outcome

Title	PK: Insulin Lispro Area Under the Concentration-Time Curve From Time Zero to 30 Minutes (AUC[0-30min]) (Part B)
Description	PK: Insulin Lispro AUC(0-30min) (Part B)
Time Frame	Predose, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 90, 120, 150, 180, 240, 300, 360, and 420 Minutes Postdose

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug LY900014 in Part B and had evaluable pharmacokinetic data. Per protocol, PK in Part B was not analyzed for 15 U Insulin Lispro (Humalog). This arm was included for only safety analysis.

Arm/Group Title	7.5 U LY900014 (Part B)	15 U LY900014 (Part B)	30 U LY900014 (Part B)
Arm/Group Description	7.5 U LY900014 given SC once in up to one of three study periods. There was a minimum three day washout between doses.	15 U LY900014 given SC once in up to one of three study periods. There was a minimum three day washout between doses.	30 U LY900014 given SC once in up to one of three study periods. There was a minimum three day washout between doses.
Measure Participants	13	13	13
Geometric Mean (Geometric Coefficient of Variation) [pmol*hour/L (pmol*hr/L)]	174 (57)	273 (51)	585 (31)

4. Secondary Outcome

Title	PK: Treprostinil Time to Maximum Concentration (Tmax) (Part A)
Description	PK: Treprostinil Tmax (Part A)
Time Frame	15, 30, 60 and 120 Minutes Postdose

Outcome Measure Data

Analysis Population Description

All participants in Part A who received study drug and had evaluable pharmacokinetic data.

Arm/Group Title	Treprostinil (Part A)
Arm/Group Description	1,000 ng treprostinil administered as a single subcutaneous (SC) injection in one of two study periods.
Measure Participants	8
Median (Full Range) [hours]	0.25

5. Secondary Outcome

Title	PK: Maximum Concentration (Cmax) of Treprostinil (Part A)
Description	PK: Cmax of Treprostinil (Part A)
Time Frame	15, 30, 60 and 120 Minutes Postdose

Outcome Measure Data

Analysis Population Description

All participants in Part A who received study drug and had evaluable pharmacokinetic data.

Arm/Group Title	Treprostinil (Part A)
Arm/Group Description	1,000 ng treprostinil administered as a single subcutaneous (SC) injection in one of two study periods.
Measure Participants	8
Geometric Mean (Geometric Coefficient of Variation) [ng/milliliter (mL)]	0.0271 (36)

Adverse Events

Time Frame	Baseline through Study Completion (up to 14 Days after Last Dose)
Adverse Event Reporting Description	All participants who received at least one dose of study drug.
Arm/Group Title	Placebo (Part A)		Treprostinil (Part A)		15 U Insulin Lispro (Part B)		7.5 U LY900014 (Part B)		15 U LY900014 (Part B)		30 U LY900014 (Part B)
Arm/Group Description	Placebo given subcutaneously (SC) once in one of two study periods. There was a minimum three day washout between doses.		1,000 ng of treprostinil given SC once in one of two study periods. There was a minimum three day washout between doses.		15 units (U) insulin lispro given SC once in up to one of three study periods. There was a minimum three day washout between doses.		7.5 U LY900014 given SC once in up to one of three study periods. There was a minimum three day washout between doses.		15 U LY900014 given SC once in up to one of three study periods. There was a minimum three day washout between doses.		30 ULY900014 given SC once in up to one of three study periods. There was a minimum three day washout between doses.
All Cause Mortality
	Placebo (Part A)		Treprostinil (Part A)		15 U Insulin Lispro (Part B)		7.5 U LY900014 (Part B)		15 U LY900014 (Part B)		30 U LY900014 (Part B)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/8 (0%)		0/6 (0%)		0/13 (0%)		0/13 (0%)		0/13 (0%)
Serious Adverse Events
	Placebo (Part A)		Treprostinil (Part A)		15 U Insulin Lispro (Part B)		7.5 U LY900014 (Part B)		15 U LY900014 (Part B)		30 U LY900014 (Part B)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/8 (0%)		0/6 (0%)		0/13 (0%)		0/13 (0%)		0/13 (0%)
Other (Not Including Serious) Adverse Events
	Placebo (Part A)		Treprostinil (Part A)		15 U Insulin Lispro (Part B)		7.5 U LY900014 (Part B)		15 U LY900014 (Part B)		30 U LY900014 (Part B)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		5/8 (62.5%)		3/6 (50%)		7/13 (53.8%)		7/13 (53.8%)		2/13 (15.4%)
General disorders
Infusion site phlebitis	0/8 (0%)	0	0/8 (0%)	0	0/6 (0%)	0	0/13 (0%)	0	2/13 (15.4%)	2	1/13 (7.7%)	1
Injection site erythema	0/8 (0%)	0	5/8 (62.5%)	5	3/6 (50%)	3	7/13 (53.8%)	7	6/13 (46.2%)	6	1/13 (7.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.