Healthy
Conditions
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.
Interventions
DRUGTreprostinil
Administered SC.
DRUGPlacebo
Administered SC.
DRUGLY900014
Administered SC.
DRUGInsulin Lispro
Administered SC.
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to 65 Years
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 * Have previously completed or withdrawn from this study or any other study investigating treprostinil or LY900014, and have previously received the investigational product * Have or used to have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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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) |
| 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
| Measure | Time frame | Description |
|---|---|---|
| PK: Treprostinil Time to Maximum Concentration (Tmax) (Part A) | 15, 30, 60 and 120 Minutes Postdose | PK: Treprostinil Tmax (Part A) |
| PK: Maximum Concentration (Cmax) of Treprostinil (Part A) | 15, 30, 60 and 120 Minutes Postdose | PK: Cmax of Treprostinil (Part A) |
Countries
Japan
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.
Participants by arm
| Arm | Count |
|---|---|
| Treprostinil or Placebo (Part A) Participants received either 1000 ng of treprostinil or matching placebo as a SC injection once in each of two study periods. | 8 |
| LY900014 or Insulin Lispro (Part B) 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. | 15 |
| Total | 23 |
Baseline characteristics
| Characteristic | Treprostinil or Placebo (Part A) | LY900014 or Insulin Lispro (Part B) | Total |
|---|---|---|---|
| Age, Continuous | 26.3 years STANDARD_DEVIATION 4.4 | 26.1 years STANDARD_DEVIATION 5.4 | 26.2 years STANDARD_DEVIATION 5 |
| Body Mass Index (BMI) | 22.57 kilograms per meter squared (kg/m²) STANDARD_DEVIATION 2 | 21.93 kilograms per meter squared (kg/m²) STANDARD_DEVIATION 2.19 | 22.15 kilograms per meter squared (kg/m²) STANDARD_DEVIATION 2.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 15 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 8 Participants | 15 Participants | 23 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Japan | 8 Participants | 15 Participants | 23 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 8 Participants | 15 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 | 0 / 6 | 0 / 13 | 0 / 13 | 0 / 13 |
| other Total, other adverse events | 0 / 8 | 5 / 8 | 3 / 6 | 7 / 13 | 7 / 13 | 2 / 13 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 0 / 6 | 0 / 13 | 0 / 13 | 0 / 13 |
Outcome results
Primary
Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
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)
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (Part A) | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 participants |
| Treprostinil (Part A) | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 participants |
| 15 U Insulin Lispro (Part B) | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 participants |
| 7.5 U LY900014 (Part B) | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 participants |
| 15 U LY900014 (Part B) | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 participants |
| 30 U LY900014 (Part B) | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 participants |
Primary
Pharmacokinetics (PK): Insulin Lispro Maximum Concentration (Cmax) (Part B)
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Part A) | Pharmacokinetics (PK): Insulin Lispro Maximum Concentration (Cmax) (Part B) | 582 picomoles/liter (pmol/L) | Geometric Coefficient of Variation 42 |
| Treprostinil (Part A) | Pharmacokinetics (PK): Insulin Lispro Maximum Concentration (Cmax) (Part B) | 956 picomoles/liter (pmol/L) | Geometric Coefficient of Variation 41 |
| 15 U Insulin Lispro (Part B) | Pharmacokinetics (PK): Insulin Lispro Maximum Concentration (Cmax) (Part B) | 2170 picomoles/liter (pmol/L) | Geometric Coefficient of Variation 30 |
Primary
PK: Insulin Lispro Area Under the Concentration-Time Curve From Time Zero to 30 Minutes (AUC[0-30min]) (Part B)
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Part A) | PK: Insulin Lispro Area Under the Concentration-Time Curve From Time Zero to 30 Minutes (AUC[0-30min]) (Part B) | 174 pmol*hour/L (pmol*hr/L) | Geometric Coefficient of Variation 57 |
| Treprostinil (Part A) | PK: Insulin Lispro Area Under the Concentration-Time Curve From Time Zero to 30 Minutes (AUC[0-30min]) (Part B) | 273 pmol*hour/L (pmol*hr/L) | Geometric Coefficient of Variation 51 |
| 15 U Insulin Lispro (Part B) | PK: Insulin Lispro Area Under the Concentration-Time Curve From Time Zero to 30 Minutes (AUC[0-30min]) (Part B) | 585 pmol*hour/L (pmol*hr/L) | Geometric Coefficient of Variation 31 |
Secondary
PK: Maximum Concentration (Cmax) of Treprostinil (Part A)
PK: Cmax of Treprostinil (Part A)
Time frame: 15, 30, 60 and 120 Minutes Postdose
Population: All participants in Part A who received study drug and had evaluable pharmacokinetic data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Part A) | PK: Maximum Concentration (Cmax) of Treprostinil (Part A) | 0.0271 ng/milliliter (mL) | Geometric Coefficient of Variation 36 |
Secondary
PK: Treprostinil Time to Maximum Concentration (Tmax) (Part A)
PK: Treprostinil Tmax (Part A)
Time frame: 15, 30, 60 and 120 Minutes Postdose
Population: All participants in Part A who received study drug and had evaluable pharmacokinetic data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo (Part A) | PK: Treprostinil Time to Maximum Concentration (Tmax) (Part A) | 0.25 hours |