A Study of LY2605541 (Insulin Peglispro) and Human Insulin Concentrations in Fat Tissue

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02109029
• Collaborator: (none)
• Enrollment: 24
• Location: 1
• Arms: 2
• Duration (Months): 11
• Patients Per Site Per Month: 2.2

Study Details

Study Description

Brief Summary

LY2605541 is an investigational drug being developed for the treatment of diabetes mellitus. This study is designed to understand how the body handles the investigational drug, and to measure the quantity of LY2605541 in fat tissue. The study has two parts. It involves intravenous (IV) infusion of the investigational drug and a procedure to measure concentrations in the fat tissue. Both parts of the study will be conducted in participants with type 1 diabetes mellitus (T1DM). Part A and B of the study might take up to 7 weeks to complete.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 1	Drug: Insulin Peglispro; Drug: Human Insulin	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Use of Open-Flow Microperfusion to Measure LY2605541 and Human Insulin Concentrations in Adipose Tissue Interstitial Fluid
• Study Start Date: Apr 1, 2014
• Actual Primary Completion Date: Mar 1, 2015
• Actual Study Completion Date: Mar 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Insulin Peglispro (LY2605541) Part A Cohort 1: (low dose) priming dose (PD) of 2.00 units (U), 0.92 U/hour (U/h) constant infusion of insulin peglispro Part A Cohort 1: (high dose) PD of 8.00 U, 4.50 U/h constant IV infusion of insulin peglispro Part A Cohort 2: (intermediate dose 1) PD of 4.00 U, 1.84/h constant IV infusion of insulin peglispro Part A Cohort 2: (intermediate dose 2) PD of 6.0 U, 2.76 U/h constant IV infusion of insulin peglispro Part B Insulin Peglispro: PD of 6.00 U, 2.76 constant IV infusion of insulin peglispro and a constant infusion of 6 pico moles per kilogram per minute (pmol/kg/min). IV infusion of sinistrin (250 mg/mL, SOC to achieve a steady state for up to 16 hours).	Drug: Insulin Peglispro; Administered IV; Other Names: LY2605541
Active Comparator: Human Insulin Constant IV infusion ( 6 pico moles per kilogram perminute [pmol/kg/min]) of human insulin for up to 36 hours. IV infusion of sinistrin (250 mg/mL, SOC to achieve a steady state for up to 16 hours).	Drug: Human Insulin; Administered IV

Outcome Measures

Primary Outcome Measures

1. Part B: Pharmacokinetics: Steady-State Concentrations in Adipose Tissue Interstitial Fluid (ISF) [16, 20, 24, and 28 hours postdose]

2. Part B: Pharmacokinetics: ISF-to-Serum Concentrations [16, 20, 24, and 28 hours postdose]

   Absolute concentration of ISF of insulin peglispro and human insulin.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Have a diagnosis of Type 1 Diabetes Mellitus (T1DM) based on medical history for at least 1 year prior to enrollment

• Have a c-peptide value ≤0.3 nanomoles per liter (nmol/L) at screening

• Have a serum creatinine value within normal limits at screening

• Have a haemoglobin A1c (HbA1c) value ≤75 millimoles per mole (mmol/mol) (9.0%) at screening

• Have a body mass index (BMI) of 20.0-30.0 kilograms per meter squared (kg/m^2), inclusive, at screening

Exclusion Criteria:

• Have known or suspected allergies or hypersensitivities to LY2605541, human insulin, sinistrin, related compounds or any components of the formulations

• Are women who are pregnant or lactating

• Have an abnormal blood pressure for the population as determined by the investigator

• Have renal insufficiency or major renal disorders

• Have proliferative retinopathy or maculopathy

• Have lipodystrophy

• Have any wound healing disorder or are prone to keloid or hypertrophic scar formation

• Have results of screening prothrombin time (PT) and international normalized ratio (INR) tests that are significantly prolonged

• Have a fasting triglycerides value > 4.52 millimoles per liter (mmol/L) (400 milligrams/deciliter (mg/dL))

• Are receiving chronic systemic or inhaled glucocorticoid or have received such therapy within the 4 weeks before dosing

• Have a total daily insulin dose greater than 1.2 units per kilogram (U/kg)

• Regular use or intended use of any over-the-counter or prescription medications or nutritional supplements that affect blood glucose or the body's sensitivity to insulin or that promote weight loss within 14 days prior to dosing

• Regular use or intended use of non-selective beta blockers

• Regular use or intended use of monoamine oxidase (MAO) inhibitors

• Are currently participating in a weight loss program or plan to do so during the course of the study

• Are unwilling to avoid excessive sun exposure, steam baths, saunas, and swimming during the study. Sun cream should be used during sun bathing for the 6-month period following the study

• Are unwilling to avoid extensive consumption of food containing inulin during the study and in the 48-hour period leading up to the clamp

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Graz		Austria	8036

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT02109029
• Other Study ID Numbers: 14873; I2R-MC-BIDP
• First Posted: Apr 9, 2014
• Last Update Posted: Mar 6, 2019
• Last Verified: Nov 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Diabetes Mellitus, Type 1; Insulin; Insulin, Globin Zinc

Study Results

Participant Flow

Arm/Group Title	Part A: Cohort 1 Insulin Peglispro Low/High	Part A: Cohort 1 Insulin Peglispro High/Low	Part A: Cohort 2 Insulin Peglispro Intermediate Dose 1 and 2	Part A: Cohort 2 Insulin Peglispro, Intermediate Dose 2 and 1	Part B: Insulin Peglispro/Human Insulin	Part B: Human Insulin/Insulin Peglispro
Arm/Group Description	Participants received a priming dose of 2.00 U and 0.92 U/ hour constant intravenous (IV) infusion of insulin peglispro for 36 hours as treatment 1 and received a priming dose of 8.00 U and 4.50/h constant infusion with at least 6 days between doses) as treatment 2.	Participants received a priming dose of 8.00 U and 4.50 U/ hour constant intravenous (IV) infusion of insulin peglispro for 36 hours as treatment 1, and an IV priming dose of 2.00 U and 0.92 U/hour constant infusion as treatment 2.	Participants received a priming dose of 4.00 U and 1.84 U/h a constant intravenous (IV) of insulin peglispro for 36 hours as treatment 1, and a 6.00 U priming dose and constant infusion of 2.76U/h of insulin peglispro as treatment 2.	Participants received a priming dose of 6.00 U and 2.76 U/h constant infusion of insulin peglispro as treatment 1, and 4.00 U and 1.84 U/h constant infusion of insulin peglispro for 36 hours as treatment 2.	Participant received a priming dose of 6.00 U and 2.76 constant intravenous infusion of insulin peglispro for 36 hours as treatment 1 and 6 pmol/kg/min constant infusion of human insulin as treatment 2.	Participant received 6 pmol/kg/min constant infusion of human insulin IV as treatment 1 and a priming dose of 6.00 U and 2.76 U/h constant infusion of insulin peglispro and a constant infusion for 36 hours as treatment 2.
Period Title: Part A
STARTED	2	2	4	4	0	0
Received One Dose of Study Drug	2	2	4	4	0	0
COMPLETED	2	2	4	4	0	0
NOT COMPLETED	0	0	0	0	0	0
Period Title: Part A
STARTED	0	0	0	0	6	6
Received at Least One Dose of Study Drug	0	0	0	0	6	6
COMPLETED	0	0	0	0	5	5
NOT COMPLETED	0	0	0	0	1	1

Baseline Characteristics

Arm/Group Title	Part A Low/High Insulin Peglispro	Part A Intermediate Insulin Peglispro	Part B	Total
Arm/Group Description	Participants received 4.00 U priming dose and 1.84 U/h constant IV infusion or 8.00 U priming dose and 4.50 U/h constant IV infusionconstant IV infusion of insulin peglispro for 36 hours with up to 2 weeks between doses.	Participants received 4.00 U priming dose and 1.84 U/h constant IV infusion or 6.00 U priming dose and 2.76U/h constant IV infusion constant IV infusion of insulin peglispro for 36 hours with up to 2 weeks between doses.	Participants first received a priming dose of 8.00 U followed by 2.76 U/h constant intravenous (IV) infusion of LY2605541 for 36 hours or 6 pmol/kg/min constant infusion of human insulin with up to 2 weeks between doses.	Total of all reporting groups
Overall Participants	4	8	12	24
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	40.0 (13.2)	39.0 (7.9)	40.9 (13.6)	40.1 (11.4)
Sex: Female, Male (Count of Participants)
Female	1 25%	0 0%	2 16.7%	3 12.5%
Male	3 75%	8 100%	10 83.3%	21 87.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%
Not Hispanic or Latino	4 100%	8 100%	12 100%	24 100%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%
White	4 100%	8 100%	12 100%	24 100%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
Austria	4 100%	8 100%	12 100%	24 100%
BMI (kilograms per meter squared (kg/m²)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms per meter squared (kg/m²)]	27.57 (2.09)	25.98 (1.87)	26.73 (1.28)	26.62 (1.65)
Body Weight (kilograms (kg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms (kg)]	83.93 (12.63)	83.80 (8.79)	83.56 (8.60)	83.70 (8.93)
HbA1c (percentage of Glycated hemoglobin) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage of Glycated hemoglobin]	7.20 (0.88)	7.51 (0.90)	7.53 (0.54)	7.47 (0.71)

Outcome Measures

1. Primary Outcome

Title	Part B: Pharmacokinetics: Steady-State Concentrations in Adipose Tissue Interstitial Fluid (ISF)
Time Frame	16, 20, 24, and 28 hours postdose

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug in Part B and had evaluable pharmacokinetic data.

Arm/Group Title	Insulin Peglispro	Human Insulin
Arm/Group Description	Participants received a priming dose of 2.00 U LY2605541 followed by a constant infusion of 0.92 U/h for up to 36 hours.	Participants received 6 pmol/kg/min constant IV infusion of human insulin for up to 36 hours
Measure Participants	10	11
Geometric Mean (Geometric Coefficient of Variation) [picomol per liter (pmol/L)]	11200 (23)	425 (15)

2. Primary Outcome

Title	Part B: Pharmacokinetics: ISF-to-Serum Concentrations
Description	Absolute concentration of ISF of insulin peglispro and human insulin.
Time Frame	16, 20, 24, and 28 hours postdose

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug in Part B and had evaluable pharmacokinetic data.

Arm/Group Title	Insulin Peglispro	Human Insulin
Arm/Group Description	Participants received a priming dose of 2.00 U LY2605541 followed by a constant infusion of 0.92 U/h for up to 36 hours.	Participants received 6 pmol/kg/min constant IV infusion of human insulin for up to 36 hours.
Measure Participants	10	11
Number [picomol per liter (pmol/L)]	1428.4	137.9

Adverse Events

Time Frame	Up to 11 months
Adverse Event Reporting Description	All participants received one dose of study drug except one participant did not receive a dose of human insulin.
Arm/Group Title	Part A: Insulin Peglispro 2U		Part A: Insulin Peglispro 4U		Part A: Insulin Peglispro 6U		Part A: Insulin Peglispro 8U		Part B: Insulin Peglispro		Part B: Human Insulin
Arm/Group Description	Participants received a priming dose of 2.00 U and 0.92 U/ hour constant intravenous (IV) infusion of insulin peglispro for 36 hours.		Participants received a priming dose of 4.00 U and 4.50 U/ hour constant intravenous (IV) infusion of insulin peglispro for 36 hours.		Participant received a priming dose of 6.00 U and 1.84 constant IV infusion of insulin peglispro respectively, for 36 hours.		Participant received a priming dose of 8.00 U and 2.76 constant IV infusion of insulin peglispro respectively, for 36 hours.		Participant received a priming dose of 6.00 U and 2.76 constant intravenous infusion of insulin peglispro for 36 hours.		Participants received 6 pmol/kg/min constant IV infusion of human insulin for up to 36 hours.
All Cause Mortality
	Part A: Insulin Peglispro 2U		Part A: Insulin Peglispro 4U		Part A: Insulin Peglispro 6U		Part A: Insulin Peglispro 8U		Part B: Insulin Peglispro		Part B: Human Insulin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Part A: Insulin Peglispro 2U		Part A: Insulin Peglispro 4U		Part A: Insulin Peglispro 6U		Part A: Insulin Peglispro 8U		Part B: Insulin Peglispro		Part B: Human Insulin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/8 (0%)		0/8 (0%)		0/4 (0%)		0/12 (0%)		0/11 (0%)
Other (Not Including Serious) Adverse Events
	Part A: Insulin Peglispro 2U		Part A: Insulin Peglispro 4U		Part A: Insulin Peglispro 6U		Part A: Insulin Peglispro 8U		Part B: Insulin Peglispro		Part B: Human Insulin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		3/8 (37.5%)		1/8 (12.5%)		0/4 (0%)		4/12 (33.3%)		2/11 (18.2%)
Gastrointestinal disorders
Nausea	0/4 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/4 (0%)	0	0/12 (0%)	0	1/11 (9.1%)	1
Immune system disorders
Drug hypersensitivity	0/4 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/4 (0%)	0	2/12 (16.7%)	2	0/11 (0%)	0
Infections and infestations
Nasopharyngitis	0/4 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/4 (0%)	0	1/12 (8.3%)	1	0/11 (0%)	0
Metabolism and nutrition disorders
Hypokalaemia	0/4 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/4 (0%)	0	1/12 (8.3%)	2	1/11 (9.1%)	2
Nervous system disorders
Headache	0/4 (0%)	0	2/8 (25%)	2	0/8 (0%)	0	0/4 (0%)	0	0/12 (0%)	0	0/11 (0%)	0
Migraine	0/4 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/4 (0%)	0	0/12 (0%)	0	1/11 (9.1%)	1
Presyncope	0/4 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/4 (0%)	0	0/12 (0%)	0	0/11 (0%)	0
Vascular disorders
Phlebitis	0/4 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/4 (0%)	0	0/12 (0%)	0	0/11 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.