Healthy Volunteers
Conditions
Brief summary
The purposes of this study are to determine: * Part A * How quickly your body absorbs, breaks down and gets rid of the different formulations of insulin lispro compared to insulin lispro alone formulation. * The safety of insulin lispro in different formulations and any side effects that might be associated with it. * Part B: * How much insulin lispro from different dose ranges is found in the bloodstream using a test insulin lispro formulation (selected from Part A). * The safety of insulin lispro in different formulations and any side effects that might be associated with it. Participants may only enroll in one part. The study is expected to last up to 10 weeks for each part.
Interventions
DRUGLispro
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
21 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
\- Overtly healthy males or females (non-childbearing potential and with absent cyclical hormonal changes), as determined by medical history and physical examination
Exclusion criteria
\- Have a fasting plasma glucose less than or equal to (≤) 4.0 millimole per liter (mmol/L) at screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A and Part B: Pharmacokinetics (PK): Area Under The Concentration Curve Zero to Infinity (AUC[0-∞]) | -30, 0 (Predose), 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 90, 120, 150,180, 240, and 300 Minutes | Primary outcome measure is based on the PK area under the concentration curve from 0 to infinity with a measurable concentration. |
Countries
Singapore
Participant flow
Pre-assignment details
Part A was a 5-period crossover study and Part B was a 4-period crossover study. A washout of 72 hours was observed between doses with a follow up within 7 to 14 days after the last dose.
Participants by arm
| Arm | Count |
|---|---|
| Part A Participants Each participant received a single SC dose of 7.0 U insulin lispro (Reference) and 4 doses of different test insulin lispro formulations (7.28 U; Tests A, B, C, and D) in one of five periods according to assigned treatment sequence 1, 2, or 3.
Sequence 1: Test A, D, C, Reference, B Sequence 2: Test B, A, Reference, C, D Sequence 3: Test Reference, Test C, B, D, A. | 24 |
| Part B Participants Each participant received a single dose of lispro SC in one of four periods according to assigned treatment sequence 1, 2, or 3. Participants received test formulation B containing 7.28 U (Units) of insulin lispro given as a single SC injection or test formulation B containing 15.47 U of insulin lispro given as a single SC injection or test formulation B containing 30.03 U of insulin lispro given as a single SC injection.
Sequence 1: 30.03 U, 7.28 U, 15.47 U, 7.28 U Sequence 2: 7.28 U, 15.47 U, 30.03 U, 15.47 U Sequence 3: 15.47 U, 30.03 U, 7.28 U, 30.03 U | 30 |
| Total | 54 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Part A and B Period 2 | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 1 |
| Part A and B Period 3 | Withdrawal by Subject | 0 | 0 | 0 | 2 | 0 | 1 |
| Part A and Part B Period 4 | Withdrawal by Subject | 0 | 0 | 0 | 2 | 0 | 1 |
Baseline characteristics
| Characteristic | Part A Participants | Part B Participants | Total |
|---|---|---|---|
| Age, Continuous | 37.7 years STANDARD_DEVIATION 11.5 | 36.8 years STANDARD_DEVIATION 9.1 | 37.2 years STANDARD_DEVIATION 10.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants | 30 Participants | 54 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 | 24 Participants | 27 Participants | 51 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 | 3 Participants | 3 Participants |
| Region of Enrollment Singapore | 24 Participants | 30 Participants | 54 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 24 Participants | 30 Participants | 54 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 | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 24 | 4 / 24 | 4 / 24 | 4 / 24 | 2 / 24 | 6 / 28 | 3 / 28 | 7 / 29 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 28 | 0 / 28 | 0 / 29 |
Outcome results
Primary
Part A and Part B: Pharmacokinetics (PK): Area Under The Concentration Curve Zero to Infinity (AUC[0-∞])
Primary outcome measure is based on the PK area under the concentration curve from 0 to infinity with a measurable concentration.
Time frame: -30, 0 (Predose), 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 90, 120, 150,180, 240, and 300 Minutes
Population: All randomized participants who were completers and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Lispro (7.0 U - Reference) | Part A and Part B: Pharmacokinetics (PK): Area Under The Concentration Curve Zero to Infinity (AUC[0-∞]) | 916 picomole*hour/Liter (pmol*hr/L) | Geometric Coefficient of Variation 21 |
| Part A: Lispro (7.28 U - Test A) | Part A and Part B: Pharmacokinetics (PK): Area Under The Concentration Curve Zero to Infinity (AUC[0-∞]) | 957 picomole*hour/Liter (pmol*hr/L) | Geometric Coefficient of Variation 22 |
| Part A: Lispro (7.28 U - Test B) | Part A and Part B: Pharmacokinetics (PK): Area Under The Concentration Curve Zero to Infinity (AUC[0-∞]) | 1020 picomole*hour/Liter (pmol*hr/L) | Geometric Coefficient of Variation 22 |
| Part A: Lispro (7.28 U - Test C) | Part A and Part B: Pharmacokinetics (PK): Area Under The Concentration Curve Zero to Infinity (AUC[0-∞]) | 972 picomole*hour/Liter (pmol*hr/L) | Geometric Coefficient of Variation 21 |
| Part A: Lispro (7.28 U - Test D) | Part A and Part B: Pharmacokinetics (PK): Area Under The Concentration Curve Zero to Infinity (AUC[0-∞]) | 971 picomole*hour/Liter (pmol*hr/L) | Geometric Coefficient of Variation 23 |
| Part B: Lispro (7.28 U - Test B) | Part A and Part B: Pharmacokinetics (PK): Area Under The Concentration Curve Zero to Infinity (AUC[0-∞]) | 864 picomole*hour/Liter (pmol*hr/L) | Geometric Coefficient of Variation 17 |
| Part B: Lispro (15.47 U - Test B) | Part A and Part B: Pharmacokinetics (PK): Area Under The Concentration Curve Zero to Infinity (AUC[0-∞]) | 2000 picomole*hour/Liter (pmol*hr/L) | Geometric Coefficient of Variation 20 |
| Part B: Lispro (30.03 U - Test B) | Part A and Part B: Pharmacokinetics (PK): Area Under The Concentration Curve Zero to Infinity (AUC[0-∞]) | 3990 picomole*hour/Liter (pmol*hr/L) | Geometric Coefficient of Variation 14 |
p-value: 0.207190% CI: [0.988, 1.1]Log Rank
p-value: 0.000590% CI: [1.06, 1.17]Log Rank
p-value: 0.012390% CI: [1.03, 1.13]Log Rank
p-value: 0.033190% CI: [1.02, 1.13]Log Rank
90% CI: [1.06, 1.16]