Trial Outcomes & Findings for A Study to Compare the Pharmacokinetics and Pharmacodynamics of LY2963016 to Lantus in Healthy Participants (NCT NCT01476345)

NCT ID: NCT01476345

Last Updated: 2014-10-07

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 80 participants
• Primary outcome timeframe: 1 hour predose up to 24 hours postdose in all treatment periods
• Results posted on: 2014-10-07

Participant Flow

This was a randomized, 2-sequence, 4-period, crossover study.

Participant milestones

Measure	LY/Lantus/LY/Lantus Sequence 1: A single 0.5 units/kilogram (U/kg) dose of LY2963016 (LY) administered subcutaneously during Periods 1 and 3. A single 0.5 U/kg dose of Lantus administered subcutaneously during Periods 2 and 4. Minimum washout interval of 7 days between each period.	Lantus/LY/Lantus/LY Sequence 2: A single 0.5 U/kg dose of Lantus administered subcutaneously during Periods 1 and 3. A single 0.5 U/kg dose of LY2963016 administered subcutaneously during Periods 2 and 4. Minimum washout interval of 7 days between each period.
Period 1 STARTED	40	40
Period 1 Received at Least 1 Dose of Study Drug	40	40
Period 1 COMPLETED	40	40
Period 1 NOT COMPLETED	0	0
Period 2 STARTED	40	40
Period 2 COMPLETED	40	40
Period 2 NOT COMPLETED	0	0
Period 3 STARTED	39	39
Period 3 COMPLETED	39	39
Period 3 NOT COMPLETED	0	0
Period 4 STARTED	39	39
Period 4 COMPLETED	39	39
Period 4 NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study to Compare the Pharmacokinetics and Pharmacodynamics of LY2963016 to Lantus in Healthy Participants

Baseline characteristics by cohort

Measure	All Participants n=80 Participants A single 0.5 units/kilogram (U/kg) dose of LY2963016 or a single 0.5 U/kg dose of Lantus administered subcutaneously followed by minimum washout interval of 7 days during 2 of 4 study periods in each sequence.
Age, Continuous	32.0 years STANDARD_DEVIATION 10.9 • n=5 Participants
Sex: Female, Male Female	24 Participants n=5 Participants
Sex: Female, Male Male	56 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	10 Participants n=5 Participants
Race (NIH/OMB) White	64 Participants n=5 Participants
Race (NIH/OMB) More than one race	6 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment South Africa	80 participants n=5 Participants

PRIMARY outcome

Timeframe: 1 hour predose up to 24 hours postdose in all treatment periods

Population: All randomized participants who received at least 1 dose of study drug and had evaluable pharmacokinetic data to calculate AUC(0-24). Participants were analyzed based on the treatment they received.

Outcome measures

Measure	LY2963016 n=79 Participants A single 0.5 units/kilogram (U/kg) dose of LY2963016 administered subcutaneously followed by minimum washout interval of 7 days during 2 of 4 study periods in each sequence.	Lantus n=80 Participants A single 0.5 U/kg dose of Lantus administered subcutaneously followed by minimum washout interval of 7 days during 2 of 4 study periods in each sequence.
Pharmacokinetics: Area Under the Concentration-Time Curve From Time Zero to 24 Hours [AUC(0-24)] of LY2963016 and Lantus	1810 picomoles*hour/Liter (pmol*h/L) Geometric Coefficient of Variation 40	1980 picomoles*hour/Liter (pmol*h/L) Geometric Coefficient of Variation 36

PRIMARY outcome

Timeframe: 1 hour predose up to 24 hours postdose in all treatment periods

Population: All randomized participants who received at least 1 dose of study drug and had evaluable pharmacokinetic data to calculate Cmax. Participants were analyzed based on the treatment they received.

Outcome measures

Measure	LY2963016 n=80 Participants A single 0.5 units/kilogram (U/kg) dose of LY2963016 administered subcutaneously followed by minimum washout interval of 7 days during 2 of 4 study periods in each sequence.	Lantus n=80 Participants A single 0.5 U/kg dose of Lantus administered subcutaneously followed by minimum washout interval of 7 days during 2 of 4 study periods in each sequence.
Pharmacokinetics: Maximum Plasma Concentration (Cmax) of LY2963016 and Lantus	112 picomoles/Liter (pmol/L) Geometric Coefficient of Variation 39	119 picomoles/Liter (pmol/L) Geometric Coefficient of Variation 34

SECONDARY outcome

Timeframe: 1 hour predose up to 24 hours postdose in all treatment periods

Population: All randomized participants who received at least 1 dose of study drug and had evaluable data to calculate Rmax. Participants were analyzed based on the treatment they received.

Rmax is the maximum infusion rate of glucose administered intravenously needed to maintain target blood glucose level and is used to measure the study drug action over time as measured by the euglycaemic clamp procedure. During the euglycaemic clamp procedure, blood glucose concentrations are held constant after the administration of LY2963016 or Lantus by adjusting the exogenous glucose infusion rate. Data presented were adjusted by the body weight.

Outcome measures

Measure	LY2963016 n=80 Participants A single 0.5 units/kilogram (U/kg) dose of LY2963016 administered subcutaneously followed by minimum washout interval of 7 days during 2 of 4 study periods in each sequence.	Lantus n=80 Participants A single 0.5 U/kg dose of Lantus administered subcutaneously followed by minimum washout interval of 7 days during 2 of 4 study periods in each sequence.
Maximum Glucose Infusion Rate (Rmax)	2.85 milligrams/kilogram/minute (mg/kg/min) Geometric Coefficient of Variation 46	2.88 milligrams/kilogram/minute (mg/kg/min) Geometric Coefficient of Variation 41

SECONDARY outcome

Timeframe: 1 hour predose up to 24 hours postdose in all treatment periods

Population: All randomized participants who received at least 1 dose of study drug and had evaluable data to calculate Gtot. Participants were analyzed based on the treatment they received.

Gtot is the total glucose infusion over the clamp duration and is used to measure the study drug action over time as measured by the euglycaemic clamp procedure. During the euglycaemic clamp procedure, blood glucose concentrations are held constant after the administration of LY2963016 or Lantus by adjusting the exogenous glucose infusion rate. Data presented were adjusted by the body weight.

Outcome measures

Measure	LY2963016 n=80 Participants A single 0.5 units/kilogram (U/kg) dose of LY2963016 administered subcutaneously followed by minimum washout interval of 7 days during 2 of 4 study periods in each sequence.	Lantus n=80 Participants A single 0.5 U/kg dose of Lantus administered subcutaneously followed by minimum washout interval of 7 days during 2 of 4 study periods in each sequence.
Total Amount of Glucose Infused (Gtot) Over the Duration of Clamp Procedure	2580 milligrams/kilogram (mg/kg) Geometric Coefficient of Variation 45	2710 milligrams/kilogram (mg/kg) Geometric Coefficient of Variation 40

Adverse Events

LY2963016

Serious events: 0 serious events

Other events: 50 other events

Deaths: 0 deaths

Lantus

Serious events: 0 serious events

Other events: 54 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	LY2963016 n=80 participants at risk A single 0.5 units/kilogram (U/kg) dose of LY2963016 administered subcutaneously followed by minimum washout interval of 7 days during 2 of 4 study periods in each sequence.	Lantus n=80 participants at risk A single 0.5 U/kg dose of Lantus administered subcutaneously followed by minimum washout interval of 7 days during 2 of 4 study periods in each sequence.
Gastrointestinal disorders Diarrhoea	5.0% 4/80 • Number of events 4	1.2% 1/80 • Number of events 1
Gastrointestinal disorders Nausea	5.0% 4/80 • Number of events 5	6.2% 5/80 • Number of events 5
General disorders Injection site erythema	5.0% 4/80 • Number of events 4	2.5% 2/80 • Number of events 3
General disorders Injection site pain	6.2% 5/80 • Number of events 5	7.5% 6/80 • Number of events 7
Injury, poisoning and procedural complications Procedural site reaction	21.2% 17/80 • Number of events 21	21.2% 17/80 • Number of events 23
Nervous system disorders Headache	18.8% 15/80 • Number of events 19	31.2% 25/80 • Number of events 27
Reproductive system and breast disorders Dysmenorrhoea	4.2% 1/24 • Number of events 1	0.00% 0/24

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

• Principal investigator is a sponsor employee Investigators agreed to delay independently publishing or disclosing data, findings or conclusions from the study except as part of a multi-center publication. Upon study publication or if the draft publication is not produced within approximately 6 months of the final report of the study results, investigators may independently publish, subject to confidential information review/redaction by sponsor. The sponsor may request publication delay up to 90 days to seek patent protection.
• Publication restrictions are in place

Restriction type: OTHER