Healthy Volunteers
Conditions
Brief summary
LY2944876 is an investigative drug for the treatment of Type 2 Diabetes Mellitus. Part A of the study will assess the safety and tolerability of single doses of LY2944876 in Japanese participants. Participation is expected to last up to about 7 weeks, not including screening. Part B of the study will investigate the safety and tolerability of multiple doses of LY2944876 in non Japanese participants. Participation is expected to last up to about 8 weeks, not including screening. All doses will be administered as injections into the fatty layer just beneath the skin. Screening is required within 28 days prior to the start of the study. All participants will attend a post study safety assessment approximately 6 weeks after their final dose.
Interventions
DRUGLY2944876
Administered SC
DRUGPlacebo
Administered SC
Sponsors
OPKO Health, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy males or female participants * Are first generation Japanese participants (Part A) or non-Japanese participants (Part B) * Have a body mass index (BMI) of 18.5 to 30 kilogram per meter square (kg/m\^2), inclusive, for Part A and a BMI of 25 to 40 kg/m\^2, inclusive, for Part B at screening * Have normal blood pressure and heart rate (after approximately 5 minutes supine and approximately 2 minutes standing) as determined by the investigator at screening
Exclusion criteria
* Have known allergies to LY2944876, related compounds or any components of the formulation, or history of significant atopy * Have an abnormality in the 12-lead electrocardiogram (ECG) at screening and/or baseline that, in the opinion of the investigator, increases the risks associated with participating in the study * Have significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal (GI), endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk when taking the study medication; or of interfering with the interpretation of data * Have a history of acute or chronic pancreatitis or elevation in serum lipase and/or amylase greater than 2 times the upper limit of normal (ULN) at screening and/or baseline * Have known or ongoing psychiatric disorders considered clinically significant in the opinion of the investigator * Have undergone any form of bariatric surgery * Have fasting blood glucose levels greater than or equal to (≥) 7 millimoles per liter (mmol/L) \[≥126 milligrams per deciliter (mg/dL)\] at screening * Have fasting triglycerides levels ≥300 mg/dL (3.4 mmol/L) at screening * Have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis, or an alanine transaminase (ALT) or aspartate aminotransferase (AST) levels greater than (\>) 2.5 times the ULN at screening and/or baseline * Have used or intend to use medications that promote weight loss, within 3 months prior to screening, for the duration 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 | Pre-dose (PRD) through Study Completion (Up to Day 40) | An SAE is any adverse event that results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. The number of participants with 1 or more SAEs considered by the investigator to be related to study drug administration is reported. A summary of SAEs and other non-serious adverse events (AEs), regardless of causality, were reported in the Reported Adverse Events module. |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetics: Area Under the Concentration Versus Time Curve - Time Zero to 168 Hours Post-dose [AUC(0-168h)] of LY2944876 | Cohorts1-3:Day1 PRD,8,12,24,32,48,56,72,96,168Hrs;Days15,28,42:Cohort4:Day1 PRD,12 Hrs;Days2,3,4,5,6 PRD;Day7 PRD,12,24,36,48,56,72,96,168 Hrs;Days21,34,49: Cohort 5:Day1 PRD,12,24,48 Hrs;Days4,6,8,10 PRD;Day12 PRD,12,24,36,48,56,72,96,168 Hrs;Day26,39,53 |
| Pharmacokinetics: Maximum Concentration (Cmax) of LY2944876 | Cohorts1-3:Day1 PRD,8,12,24,32,48,56,72,96,168Hrs;Days15,28,42:Cohort4:Day1 PRD,12 Hrs;Days2,3,4,5,6 PRD;Day7 PRD,12,24,36,48,56,72,96,168 Hrs;Days21,34,49: Cohort 5:Day1 PRD,12,24,48 Hrs;Days4,6,8,10 PRD;Day12 PRD,12,24,36,48,56,72,96,168 Hrs;Day26,39,53 |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Part A / Cohorts 1-3 - Placebo Placebo, Single Dose Administered SC | 6 |
| Part A / Cohort 1 - 10 mg LY2944876 LY2944876 10 mg, Single Dose Administered SC | 6 |
| Part A / Cohort 2 - 30 mg LY2944876 LY2944876 30 mg, Single Dose Administered SC | 6 |
| Part A / Cohort 3 - 50 mg LY2944876 LY2944876 50 mg, Single Dose Administered SC | 6 |
| Part B / Cohort 4 - Placebo Placebo Administered QD SC, Days 1-7 | 4 |
| Part B / Cohort 4 - 40 mg LY2944876 LY2944876 40 mg, Administered QD SC, Days 1-7 | 12 |
| Part B / Cohort 5 - Placebo Placebo, Administered QD SC, Days 1, 4 and 6. | 2 |
| Part B / Cohort 5 - 15-60 mg Titrated LY2944876 LY2944876 Administered QD SC 15 mg on Day 1, 30 mg on Day 4 and up to 60 mg on Day 6. | 6 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 2 |
| Overall Study | Dose Termination Criteria Met | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 4 |
Baseline characteristics
| Characteristic | Part A / Cohorts 1-3 - Placebo | Part A / Cohort 1 - 10 mg LY2944876 | Part A / Cohort 2 - 30 mg LY2944876 | Part A / Cohort 3 - 50 mg LY2944876 | Total | Part B / Cohort 4 - Placebo | Part B / Cohort 4 - 40 mg LY2944876 | Part B / Cohort 5 - Placebo | Part B / Cohort 5 - 15-60 mg Titrated LY2944876 |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous Cohorts 1-3 | 29.2 Years STANDARD_DEVIATION 5.4 | 33.2 Years STANDARD_DEVIATION 5.8 | 29.5 Years STANDARD_DEVIATION 3.9 | 29.2 Years STANDARD_DEVIATION 3.5 | 30.3 Years STANDARD_DEVIATION 4.8 | — | — | — | — |
| Age, Continuous Cohorts 4-5 | — | — | — | — | 47.3 Years STANDARD_DEVIATION 15.6 | 47.5 Years STANDARD_DEVIATION 18.2 | 46.3 Years STANDARD_DEVIATION 16.4 | 56.5 Years STANDARD_DEVIATION 7.8 | 46.3 Years STANDARD_DEVIATION 16.6 |
| Race/Ethnicity, Customized Asian | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 25 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 23 Participants | 4 Participants | 11 Participants | 2 Participants | 6 Participants |
| Region of Enrollment United Kingdom | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 48 Participants | 4 Participants | 12 Participants | 2 Participants | 6 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 8 Participants | 2 Participants | 3 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 40 Participants | 2 Participants | 9 Participants | 1 Participants | 4 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 | 0 / 6 | 4 / 6 | 4 / 6 | 6 / 6 | 4 / 4 | 12 / 12 | 2 / 2 | 6 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 4 | 0 / 12 | 0 / 2 | 0 / 6 |
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
An SAE is any adverse event that results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. The number of participants with 1 or more SAEs considered by the investigator to be related to study drug administration is reported. A summary of SAEs and other non-serious adverse events (AEs), regardless of causality, were reported in the Reported Adverse Events module.
Time frame: Pre-dose (PRD) through Study Completion (Up to Day 40)
Population: All enrolled participants, whether or not they completed all protocol requirements.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohorts 1-3 - Placebo | 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 |
| Cohort 1 - 10 mg LY2944876 | 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 |
| Cohort 2 - 30 mg LY2944876 | 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 |
| Cohort 3 - 50 mg LY2944876 | 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 |
| Cohort 4 - Placebo | 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 |
| Cohort 4 - 40 mg LY2944876 | 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 |
| Cohort 5 - Placebo | 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 |
| Cohort 5 - 15-60 mg Titrated LY2944876 | 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 |
Secondary
Pharmacokinetics: Area Under the Concentration Versus Time Curve - Time Zero to 168 Hours Post-dose [AUC(0-168h)] of LY2944876
Time frame: Cohorts1-3:Day1 PRD,8,12,24,32,48,56,72,96,168Hrs;Days15,28,42:Cohort4:Day1 PRD,12 Hrs;Days2,3,4,5,6 PRD;Day7 PRD,12,24,36,48,56,72,96,168 Hrs;Days21,34,49: Cohort 5:Day1 PRD,12,24,48 Hrs;Days4,6,8,10 PRD;Day12 PRD,12,24,36,48,56,72,96,168 Hrs;Day26,39,53
Population: All randomized participants receiving at least one dose of the investigational product and had evaluable AUC data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohorts 1-3 - Placebo | Pharmacokinetics: Area Under the Concentration Versus Time Curve - Time Zero to 168 Hours Post-dose [AUC(0-168h)] of LY2944876 | 105000 nanograms∙hours/milliliters (ng∙h/mL) | Geometric Coefficient of Variation 32 |
| Cohort 1 - 10 mg LY2944876 | Pharmacokinetics: Area Under the Concentration Versus Time Curve - Time Zero to 168 Hours Post-dose [AUC(0-168h)] of LY2944876 | 307000 nanograms∙hours/milliliters (ng∙h/mL) | Geometric Coefficient of Variation 38 |
| Cohort 2 - 30 mg LY2944876 | Pharmacokinetics: Area Under the Concentration Versus Time Curve - Time Zero to 168 Hours Post-dose [AUC(0-168h)] of LY2944876 | 495000 nanograms∙hours/milliliters (ng∙h/mL) | Geometric Coefficient of Variation 34 |
| Cohort 3 - 50 mg LY2944876 | Pharmacokinetics: Area Under the Concentration Versus Time Curve - Time Zero to 168 Hours Post-dose [AUC(0-168h)] of LY2944876 | 1789000 nanograms∙hours/milliliters (ng∙h/mL) | Geometric Coefficient of Variation 15 |
| Cohort 4 - Placebo | Pharmacokinetics: Area Under the Concentration Versus Time Curve - Time Zero to 168 Hours Post-dose [AUC(0-168h)] of LY2944876 | 803000 nanograms∙hours/milliliters (ng∙h/mL) | Geometric Coefficient of Variation 24 |
Secondary
Pharmacokinetics: Maximum Concentration (Cmax) of LY2944876
Time frame: Cohorts1-3:Day1 PRD,8,12,24,32,48,56,72,96,168Hrs;Days15,28,42:Cohort4:Day1 PRD,12 Hrs;Days2,3,4,5,6 PRD;Day7 PRD,12,24,36,48,56,72,96,168 Hrs;Days21,34,49: Cohort 5:Day1 PRD,12,24,48 Hrs;Days4,6,8,10 PRD;Day12 PRD,12,24,36,48,56,72,96,168 Hrs;Day26,39,53
Population: All randomized participants receiving at least one dose of the investigational product and had evaluable Cmax data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohorts 1-3 - Placebo | Pharmacokinetics: Maximum Concentration (Cmax) of LY2944876 | 790 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 33 |
| Cohort 1 - 10 mg LY2944876 | Pharmacokinetics: Maximum Concentration (Cmax) of LY2944876 | 2360 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 36 |
| Cohort 2 - 30 mg LY2944876 | Pharmacokinetics: Maximum Concentration (Cmax) of LY2944876 | 3640 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 35 |
| Cohort 3 - 50 mg LY2944876 | Pharmacokinetics: Maximum Concentration (Cmax) of LY2944876 | 11700 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 26 |
| Cohort 4 - Placebo | Pharmacokinetics: Maximum Concentration (Cmax) of LY2944876 | 5470 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 22 |