Trial Outcomes & Findings for Bioequivalence of Two Lispro Formulations (NCT NCT01133392)

Last Updated: 2014-12-30

Results Overview

Primary outcome measure is based on the pharmacokinetic area under the concentration-time curve from time 0 to the last time point with a measurable concentration.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

41 participants

Primary outcome timeframe

0 up to 8 hours post dose

Results posted on

2014-12-30

Participant Flow

41 participants were enrolled into the study. 3 participants discontinued due to subject decision prior to receiving treatment.

Participant milestones

Participant milestones
Measure	Insulin Lispro Dosing Sequence ABAB Each participant was administered insulin lispro A formulation (Treatment A, test - 2 occasions) and insulin lispro B formulation (Treatment B, reference - 2 occasions) in the dosing sequence ABAB. There was an interval of approximately 4 to 7 days between doses.	Insulin Lispro Dosing Sequence BABA Each participant was administered insulin lispro A formulation (Treatment A, test - 2 occasions) and insulin lispro B formulation (Treatment B, reference - 2 occasions) in the dosing sequence BABA. There was an interval of approximately 4 to 7 days between doses.
First Intervention (1 Day ) STARTED	20	18
First Intervention (1 Day ) COMPLETED	20	18
First Intervention (1 Day ) NOT COMPLETED	0	0
Interval Between Dosing (4-7 Days) STARTED	20	17
Interval Between Dosing (4-7 Days) COMPLETED	20	16
Interval Between Dosing (4-7 Days) NOT COMPLETED	0	1
Second Intervention (1 Day) STARTED	20	17
Second Intervention (1 Day) COMPLETED	20	17
Second Intervention (1 Day) NOT COMPLETED	0	0
Third Intervention (1 Day) STARTED	20	17
Third Intervention (1 Day) COMPLETED	20	17
Third Intervention (1 Day) NOT COMPLETED	0	0
Fourth Intervention (1 Day) STARTED	20	16
Fourth Intervention (1 Day) COMPLETED	20	16
Fourth Intervention (1 Day) NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Insulin Lispro Dosing Sequence ABAB Each participant was administered insulin lispro A formulation (Treatment A, test - 2 occasions) and insulin lispro B formulation (Treatment B, reference - 2 occasions) in the dosing sequence ABAB. There was an interval of approximately 4 to 7 days between doses.	Insulin Lispro Dosing Sequence BABA Each participant was administered insulin lispro A formulation (Treatment A, test - 2 occasions) and insulin lispro B formulation (Treatment B, reference - 2 occasions) in the dosing sequence BABA. There was an interval of approximately 4 to 7 days between doses.
Interval Between Dosing (4-7 Days) Withdrawal by Subject	0	1
Interval Between Dosing (4-7 Days) Protocol Violation	0	1

Baseline Characteristics

Bioequivalence of Two Lispro Formulations

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Insulin Lispro Dosing Sequence ABAB n=20 Participants Each participant was administered insulin lispro A formulation (Treatment A, test - 2 occasions) and insulin lispro B formulation (Treatment B, reference - 2 occasions) in the dosing sequence ABAB.	Insulin Lispro Dosing Sequence BABA n=18 Participants Each participant was administered insulin lispro A formulation (Treatment A, test - 2 occasions) and insulin lispro B formulation (Treatment B, reference - 2 occasions) in the dosing sequence BABA.	Total n=38 Participants Total of all reporting groups
Age, Continuous	30.4 years STANDARD_DEVIATION 7.2 • n=5 Participants	34.6 years STANDARD_DEVIATION 6.4 • n=7 Participants	32.4 years STANDARD_DEVIATION 7.1 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Sex: Female, Male Male	20 Participants n=5 Participants	16 Participants n=7 Participants	36 Participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	20 participants n=5 Participants	18 participants n=7 Participants	38 participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Region of Enrollment Singapore	20 participants n=5 Participants	18 participants n=7 Participants	38 participants n=5 Participants

PRIMARY outcome

Timeframe: 0 up to 8 hours post dose

Population: All participants who had at least one study treatment and had evaluable pharmacokinetic (PK) data.

Primary outcome measure is based on the pharmacokinetic area under the concentration-time curve from time 0 to the last time point with a measurable concentration.

Outcome measures

Outcome measures
Measure	Insulin Lispro A n=37 Participants 20 units (U) administered subcutaneously (SC)	Insulin Lispro B n=38 Participants 20 units (U) administered subcutaneously (SC)
Pharmacokinetic Parameter: Area Under the Serum Insulin Concentration Versus Time Curve From Time Zero to the Last Time Point With a Measurable Concentration [AUC0-tlast]	1920 picomolehour/liter (pmolh/L) Geometric Coefficient of Variation 20	1940 picomolehour/liter (pmolh/L) Geometric Coefficient of Variation 20

SECONDARY outcome

Timeframe: 0 to 8 hours post dose

Population: All participants who had at least one study treatment and had evaluable PK data.

The maximum observed insulin lispro concentration following dosing.

Outcome measures

Outcome measures
Measure	Insulin Lispro A n=37 Participants 20 units (U) administered subcutaneously (SC)	Insulin Lispro B n=38 Participants 20 units (U) administered subcutaneously (SC)
Pharmacokinetic Parameter: Maximum Serum Insulin Concentration [Cmax]	819 picomole/liter (pmol/L) Geometric Coefficient of Variation 32	887 picomole/liter (pmol/L) Geometric Coefficient of Variation 34

SECONDARY outcome

Timeframe: 0 to 8 hours post dose

Population: All participants who had at least one study treatment and had evaluable pharmacodynamic (PD) data.

The maximum observed glucose infusion rate during the euglycemic clamp procedure.

Outcome measures

Outcome measures
Measure	Insulin Lispro A n=37 Participants 20 units (U) administered subcutaneously (SC)	Insulin Lispro B n=38 Participants 20 units (U) administered subcutaneously (SC)
Pharmacodynamic Parameter: Maximum Glucose Infusion Rate (Rmax)	544 milligrams per minute (mg/min) Geometric Coefficient of Variation 23	539 milligrams per minute (mg/min) Geometric Coefficient of Variation 27

SECONDARY outcome

Timeframe: 0 to 8 hours post dose

Population: All participants who had at least one study treatment and had evaluable PD data.

Time of maximal glucose infusion rate.

Outcome measures

Outcome measures
Measure	Insulin Lispro A n=37 Participants 20 units (U) administered subcutaneously (SC)	Insulin Lispro B n=38 Participants 20 units (U) administered subcutaneously (SC)
Pharmacodynamic Parameter: Time of Maximum Glucose Infusion Rate (tRmax)	2.11 hours Geometric Coefficient of Variation 49	2.00 hours Geometric Coefficient of Variation 56

SECONDARY outcome

Timeframe: 0 to 8 hours post dose

Population: All participants who had at least one study treatment and had evaluable PD data.

The total amount of glucose infused during the euglycemic clamp procedure.

Outcome measures

Outcome measures
Measure	Insulin Lispro A n=37 Participants 20 units (U) administered subcutaneously (SC)	Insulin Lispro B n=38 Participants 20 units (U) administered subcutaneously (SC)
Pharmacodynamic Parameter: Total Amount of Glucose Infused (Gtot)	125 grams (g) Geometric Coefficient of Variation 25	123 grams (g) Geometric Coefficient of Variation 30

Adverse Events

Insulin Lispro A

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Insulin Lispro B

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Insulin Lispro A n=37 participants at risk Insulin lispro A formulation (Treatment A, test - 2 occasions)	Insulin Lispro B n=38 participants at risk Insulin lispro B formulation (Treatment B, reference - 2 occasions)
Eye disorders Eye discharge	0.00% 0/37 38 participants were randomly assigned to treatment, 38 participants received at least 1 dose of study drug, 36 participants completed all 4 periods of the study. One participant only completed 1 insulin lispro B period and then discontinued. This participant did not complete the insulin lispro A periods.	2.6% 1/38 • Number of events 1 38 participants were randomly assigned to treatment, 38 participants received at least 1 dose of study drug, 36 participants completed all 4 periods of the study. One participant only completed 1 insulin lispro B period and then discontinued. This participant did not complete the insulin lispro A periods.
Gastrointestinal disorders Diarrhoea	0.00% 0/37 38 participants were randomly assigned to treatment, 38 participants received at least 1 dose of study drug, 36 participants completed all 4 periods of the study. One participant only completed 1 insulin lispro B period and then discontinued. This participant did not complete the insulin lispro A periods.	2.6% 1/38 • Number of events 1 38 participants were randomly assigned to treatment, 38 participants received at least 1 dose of study drug, 36 participants completed all 4 periods of the study. One participant only completed 1 insulin lispro B period and then discontinued. This participant did not complete the insulin lispro A periods.
General disorders Catheter site haematoma	13.5% 5/37 • Number of events 5 38 participants were randomly assigned to treatment, 38 participants received at least 1 dose of study drug, 36 participants completed all 4 periods of the study. One participant only completed 1 insulin lispro B period and then discontinued. This participant did not complete the insulin lispro A periods.	10.5% 4/38 • Number of events 6 38 participants were randomly assigned to treatment, 38 participants received at least 1 dose of study drug, 36 participants completed all 4 periods of the study. One participant only completed 1 insulin lispro B period and then discontinued. This participant did not complete the insulin lispro A periods.
General disorders Catheter site pain	2.7% 1/37 • Number of events 1 38 participants were randomly assigned to treatment, 38 participants received at least 1 dose of study drug, 36 participants completed all 4 periods of the study. One participant only completed 1 insulin lispro B period and then discontinued. This participant did not complete the insulin lispro A periods.	2.6% 1/38 • Number of events 1 38 participants were randomly assigned to treatment, 38 participants received at least 1 dose of study drug, 36 participants completed all 4 periods of the study. One participant only completed 1 insulin lispro B period and then discontinued. This participant did not complete the insulin lispro A periods.
General disorders Catheter site swelling	0.00% 0/37 38 participants were randomly assigned to treatment, 38 participants received at least 1 dose of study drug, 36 participants completed all 4 periods of the study. One participant only completed 1 insulin lispro B period and then discontinued. This participant did not complete the insulin lispro A periods.	5.3% 2/38 • Number of events 2 38 participants were randomly assigned to treatment, 38 participants received at least 1 dose of study drug, 36 participants completed all 4 periods of the study. One participant only completed 1 insulin lispro B period and then discontinued. This participant did not complete the insulin lispro A periods.
General disorders Injection site pain	5.4% 2/37 • Number of events 2 38 participants were randomly assigned to treatment, 38 participants received at least 1 dose of study drug, 36 participants completed all 4 periods of the study. One participant only completed 1 insulin lispro B period and then discontinued. This participant did not complete the insulin lispro A periods.	0.00% 0/38 38 participants were randomly assigned to treatment, 38 participants received at least 1 dose of study drug, 36 participants completed all 4 periods of the study. One participant only completed 1 insulin lispro B period and then discontinued. This participant did not complete the insulin lispro A periods.
General disorders Injection site swelling	2.7% 1/37 • Number of events 1 38 participants were randomly assigned to treatment, 38 participants received at least 1 dose of study drug, 36 participants completed all 4 periods of the study. One participant only completed 1 insulin lispro B period and then discontinued. This participant did not complete the insulin lispro A periods.	0.00% 0/38 38 participants were randomly assigned to treatment, 38 participants received at least 1 dose of study drug, 36 participants completed all 4 periods of the study. One participant only completed 1 insulin lispro B period and then discontinued. This participant did not complete the insulin lispro A periods.
Injury, poisoning and procedural complications Contusion	2.7% 1/37 • Number of events 1 38 participants were randomly assigned to treatment, 38 participants received at least 1 dose of study drug, 36 participants completed all 4 periods of the study. One participant only completed 1 insulin lispro B period and then discontinued. This participant did not complete the insulin lispro A periods.	0.00% 0/38 38 participants were randomly assigned to treatment, 38 participants received at least 1 dose of study drug, 36 participants completed all 4 periods of the study. One participant only completed 1 insulin lispro B period and then discontinued. This participant did not complete the insulin lispro A periods.
Injury, poisoning and procedural complications Excoriation	2.7% 1/37 • Number of events 1 38 participants were randomly assigned to treatment, 38 participants received at least 1 dose of study drug, 36 participants completed all 4 periods of the study. One participant only completed 1 insulin lispro B period and then discontinued. This participant did not complete the insulin lispro A periods.	0.00% 0/38 38 participants were randomly assigned to treatment, 38 participants received at least 1 dose of study drug, 36 participants completed all 4 periods of the study. One participant only completed 1 insulin lispro B period and then discontinued. This participant did not complete the insulin lispro A periods.
Injury, poisoning and procedural complications Fall	2.7% 1/37 • Number of events 1 38 participants were randomly assigned to treatment, 38 participants received at least 1 dose of study drug, 36 participants completed all 4 periods of the study. One participant only completed 1 insulin lispro B period and then discontinued. This participant did not complete the insulin lispro A periods.	0.00% 0/38 38 participants were randomly assigned to treatment, 38 participants received at least 1 dose of study drug, 36 participants completed all 4 periods of the study. One participant only completed 1 insulin lispro B period and then discontinued. This participant did not complete the insulin lispro A periods.
Injury, poisoning and procedural complications Head injury	0.00% 0/37 38 participants were randomly assigned to treatment, 38 participants received at least 1 dose of study drug, 36 participants completed all 4 periods of the study. One participant only completed 1 insulin lispro B period and then discontinued. This participant did not complete the insulin lispro A periods.	2.6% 1/38 • Number of events 1 38 participants were randomly assigned to treatment, 38 participants received at least 1 dose of study drug, 36 participants completed all 4 periods of the study. One participant only completed 1 insulin lispro B period and then discontinued. This participant did not complete the insulin lispro A periods.
Injury, poisoning and procedural complications Procedural site reaction	2.7% 1/37 • Number of events 3 38 participants were randomly assigned to treatment, 38 participants received at least 1 dose of study drug, 36 participants completed all 4 periods of the study. One participant only completed 1 insulin lispro B period and then discontinued. This participant did not complete the insulin lispro A periods.	2.6% 1/38 • Number of events 2 38 participants were randomly assigned to treatment, 38 participants received at least 1 dose of study drug, 36 participants completed all 4 periods of the study. One participant only completed 1 insulin lispro B period and then discontinued. This participant did not complete the insulin lispro A periods.
Injury, poisoning and procedural complications Thermal burn	0.00% 0/37 38 participants were randomly assigned to treatment, 38 participants received at least 1 dose of study drug, 36 participants completed all 4 periods of the study. One participant only completed 1 insulin lispro B period and then discontinued. This participant did not complete the insulin lispro A periods.	2.6% 1/38 • Number of events 1 38 participants were randomly assigned to treatment, 38 participants received at least 1 dose of study drug, 36 participants completed all 4 periods of the study. One participant only completed 1 insulin lispro B period and then discontinued. This participant did not complete the insulin lispro A periods.
Investigations Blood urine present	2.7% 1/37 • Number of events 1 38 participants were randomly assigned to treatment, 38 participants received at least 1 dose of study drug, 36 participants completed all 4 periods of the study. One participant only completed 1 insulin lispro B period and then discontinued. This participant did not complete the insulin lispro A periods.	0.00% 0/38 38 participants were randomly assigned to treatment, 38 participants received at least 1 dose of study drug, 36 participants completed all 4 periods of the study. One participant only completed 1 insulin lispro B period and then discontinued. This participant did not complete the insulin lispro A periods.
Musculoskeletal and connective tissue disorders Back pain	2.7% 1/37 • Number of events 1 38 participants were randomly assigned to treatment, 38 participants received at least 1 dose of study drug, 36 participants completed all 4 periods of the study. One participant only completed 1 insulin lispro B period and then discontinued. This participant did not complete the insulin lispro A periods.	0.00% 0/38 38 participants were randomly assigned to treatment, 38 participants received at least 1 dose of study drug, 36 participants completed all 4 periods of the study. One participant only completed 1 insulin lispro B period and then discontinued. This participant did not complete the insulin lispro A periods.
Musculoskeletal and connective tissue disorders Joint swelling	2.7% 1/37 • Number of events 1 38 participants were randomly assigned to treatment, 38 participants received at least 1 dose of study drug, 36 participants completed all 4 periods of the study. One participant only completed 1 insulin lispro B period and then discontinued. This participant did not complete the insulin lispro A periods.	0.00% 0/38 38 participants were randomly assigned to treatment, 38 participants received at least 1 dose of study drug, 36 participants completed all 4 periods of the study. One participant only completed 1 insulin lispro B period and then discontinued. This participant did not complete the insulin lispro A periods.
Musculoskeletal and connective tissue disorders Myalgia	2.7% 1/37 • Number of events 1 38 participants were randomly assigned to treatment, 38 participants received at least 1 dose of study drug, 36 participants completed all 4 periods of the study. One participant only completed 1 insulin lispro B period and then discontinued. This participant did not complete the insulin lispro A periods.	2.6% 1/38 • Number of events 1 38 participants were randomly assigned to treatment, 38 participants received at least 1 dose of study drug, 36 participants completed all 4 periods of the study. One participant only completed 1 insulin lispro B period and then discontinued. This participant did not complete the insulin lispro A periods.
Nervous system disorders Dizziness	2.7% 1/37 • Number of events 1 38 participants were randomly assigned to treatment, 38 participants received at least 1 dose of study drug, 36 participants completed all 4 periods of the study. One participant only completed 1 insulin lispro B period and then discontinued. This participant did not complete the insulin lispro A periods.	0.00% 0/38 38 participants were randomly assigned to treatment, 38 participants received at least 1 dose of study drug, 36 participants completed all 4 periods of the study. One participant only completed 1 insulin lispro B period and then discontinued. This participant did not complete the insulin lispro A periods.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/37 38 participants were randomly assigned to treatment, 38 participants received at least 1 dose of study drug, 36 participants completed all 4 periods of the study. One participant only completed 1 insulin lispro B period and then discontinued. This participant did not complete the insulin lispro A periods.	2.6% 1/38 • Number of events 1 38 participants were randomly assigned to treatment, 38 participants received at least 1 dose of study drug, 36 participants completed all 4 periods of the study. One participant only completed 1 insulin lispro B period and then discontinued. This participant did not complete the insulin lispro A periods.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/37 38 participants were randomly assigned to treatment, 38 participants received at least 1 dose of study drug, 36 participants completed all 4 periods of the study. One participant only completed 1 insulin lispro B period and then discontinued. This participant did not complete the insulin lispro A periods.	5.3% 2/38 • Number of events 2 38 participants were randomly assigned to treatment, 38 participants received at least 1 dose of study drug, 36 participants completed all 4 periods of the study. One participant only completed 1 insulin lispro B period and then discontinued. This participant did not complete the insulin lispro A periods.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/37 38 participants were randomly assigned to treatment, 38 participants received at least 1 dose of study drug, 36 participants completed all 4 periods of the study. One participant only completed 1 insulin lispro B period and then discontinued. This participant did not complete the insulin lispro A periods.	2.6% 1/38 • Number of events 1 38 participants were randomly assigned to treatment, 38 participants received at least 1 dose of study drug, 36 participants completed all 4 periods of the study. One participant only completed 1 insulin lispro B period and then discontinued. This participant did not complete the insulin lispro A periods.
Vascular disorders Flushing	0.00% 0/37 38 participants were randomly assigned to treatment, 38 participants received at least 1 dose of study drug, 36 participants completed all 4 periods of the study. One participant only completed 1 insulin lispro B period and then discontinued. This participant did not complete the insulin lispro A periods.	2.6% 1/38 • Number of events 1 38 participants were randomly assigned to treatment, 38 participants received at least 1 dose of study drug, 36 participants completed all 4 periods of the study. One participant only completed 1 insulin lispro B period and then discontinued. This participant did not complete the insulin lispro A periods.