Trial Outcomes & Findings for A Study of U-500 Insulin (LY041001) in Participants With Type 2 Diabetes (NCT NCT02588950)
NCT ID: NCT02588950
Last Updated: 2023-10-23
Results Overview
Part A: Pharmacokinetics (PK): Time to Maximum Drug Concentration (Tmax) of U-500R.
Recruitment status
TERMINATED
Study phase
PHASE1
Target enrollment
11 participants
Primary outcome timeframe
Period 1 and 2: -0.5, 0, 0.5, 1, 2, 3, 4, 6, 7, 8, 12, 16, 24 hours (h) post dose
Results posted on
2023-10-23
Participant Flow
Two parts study with Part A (Periods 1 \& 2) \& Part B (Period 3). Part A:Participants received study drug either by subcutaneous(SC) or continuous subcutaneous insulin infusion (CSII) as per the dosing sequence. Part B: Participants received study drug via SC injection either twice daily (BID) or three times daily (TID) as per the dosing sequence.
Participant milestones
| Measure |
Sequence 1
Participants received 100- Unit (U) of human regular U-500 insulin (U-500R) by subcutaneous (SC) injection in period 1 and 4.25 U/hour U-500R basal infusion for 12 hours prior to and during the 24 hour clamp plus a 100-U of U-500R via continuous SC insulin infusion (CSII) in period 2 and U-500R administered thrice daily via SC injection in period 3.
|
Sequence 2
Participants received 4.25 U/hour U-500R basal infusion for 12 hours prior to and during the 24 hour clamp plus a 100-U of U-500R via continuous SC insulin infusion (CSII) in period 1 and 100-U of human regular U-500 insulin (U-500R) by subcutaneous (SC) injection in period 2 and U-500R administered twice daily via SC injection in period 3.
|
Sequence 3
Participants received 100-U of human regular U-500 insulin (U-500R) by subcutaneous (SC) injection in period 1 and 4.25 U/hour U-500R basal infusion for 12 hours prior to and during the 24 hour clamp plus a 100-U of U-500R via continuous SC insulin infusion (CSII) in period 2 and U-500R administered twice daily via SC injection in period 3.
|
Sequence 4
Participants received 4.25 U/hour U-500R basal infusion for 12 hours prior to and during the 24 hour clamp plus a 100-U of U-500R via continuous SC insulin infusion (CSII) in period 1 and 100-U of human regular U-500 insulin (U-500R) by subcutaneous (SC) injection in period 2 and U-500R administered thrice daily via SC injection in period 3.
|
|---|---|---|---|---|
|
Period 1 (Part A)
STARTED
|
3
|
2
|
3
|
3
|
|
Period 1 (Part A)
Received at Least One Dose of Study Drug
|
3
|
2
|
3
|
3
|
|
Period 1 (Part A)
COMPLETED
|
3
|
2
|
3
|
3
|
|
Period 1 (Part A)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Period 2 (Part A)
STARTED
|
3
|
2
|
3
|
3
|
|
Period 2 (Part A)
COMPLETED
|
3
|
2
|
2
|
3
|
|
Period 2 (Part A)
NOT COMPLETED
|
0
|
0
|
1
|
0
|
|
Period 3 (Part B)
STARTED
|
3
|
2
|
2
|
3
|
|
Period 3 (Part B)
COMPLETED
|
3
|
2
|
2
|
2
|
|
Period 3 (Part B)
NOT COMPLETED
|
0
|
0
|
0
|
1
|
Reasons for withdrawal
| Measure |
Sequence 1
Participants received 100- Unit (U) of human regular U-500 insulin (U-500R) by subcutaneous (SC) injection in period 1 and 4.25 U/hour U-500R basal infusion for 12 hours prior to and during the 24 hour clamp plus a 100-U of U-500R via continuous SC insulin infusion (CSII) in period 2 and U-500R administered thrice daily via SC injection in period 3.
|
Sequence 2
Participants received 4.25 U/hour U-500R basal infusion for 12 hours prior to and during the 24 hour clamp plus a 100-U of U-500R via continuous SC insulin infusion (CSII) in period 1 and 100-U of human regular U-500 insulin (U-500R) by subcutaneous (SC) injection in period 2 and U-500R administered twice daily via SC injection in period 3.
|
Sequence 3
Participants received 100-U of human regular U-500 insulin (U-500R) by subcutaneous (SC) injection in period 1 and 4.25 U/hour U-500R basal infusion for 12 hours prior to and during the 24 hour clamp plus a 100-U of U-500R via continuous SC insulin infusion (CSII) in period 2 and U-500R administered twice daily via SC injection in period 3.
|
Sequence 4
Participants received 4.25 U/hour U-500R basal infusion for 12 hours prior to and during the 24 hour clamp plus a 100-U of U-500R via continuous SC insulin infusion (CSII) in period 1 and 100-U of human regular U-500 insulin (U-500R) by subcutaneous (SC) injection in period 2 and U-500R administered thrice daily via SC injection in period 3.
|
|---|---|---|---|---|
|
Period 2 (Part A)
Withdrawal by Subject
|
0
|
0
|
1
|
0
|
|
Period 3 (Part B)
Withdrawal by Subject
|
0
|
0
|
0
|
1
|
Baseline Characteristics
A Study of U-500 Insulin (LY041001) in Participants With Type 2 Diabetes
Baseline characteristics by cohort
| Measure |
Overall
n=11 Participants
Participants received 100-U of human regular U-500 insulin (U-500R) by subcutaneous (SC) injection or 4.25 U/hour U-500R basal infusion for 12 hours prior to and during the 24 hour clamp plus a 100-U of U-500R via continuous SC insulin infusion (CSII) in Part A (periods 1 \& 2), and U-500R administered twice or thrice daily via SC injection in part B (period 3) as per the dosing sequence in each period.
|
|---|---|
|
Age, Continuous
|
56.2 years
STANDARD_DEVIATION 7.3 • n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
4 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
7 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 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
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
6 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Body mass index
|
39.63 Kilogram per square meter (kg/m^2)
STANDARD_DEVIATION 8.59 • n=5 Participants
|
PRIMARY outcome
Timeframe: Period 1 and 2: -0.5, 0, 0.5, 1, 2, 3, 4, 6, 7, 8, 12, 16, 24 hours (h) post dosePopulation: All randomized participants who received at least one dose of study drug and had evaluable PK data in part A.
Part A: Pharmacokinetics (PK): Time to Maximum Drug Concentration (Tmax) of U-500R.
Outcome measures
| Measure |
100-U Bolus U-500R SC
n=11 Participants
Participants received 100-U of human regular U-500 insulin (U-500R) by subcutaneous (SC) injection.
|
100-U Bolus U-500R CSII
n=11 Participants
Participants received 4.25 U/hour U-500R basal infusion for 12 hours prior to and during the 24 hour clamp plus a 100-U of U-500R via continuous SC insulin infusion (CSII).
|
|---|---|---|
|
Part A: Pharmacokinetics (PK): Time to Maximum Drug Concentration (Tmax) of U-500R
|
6 Hours (h)
Interval 0.5 to 8.0
|
5 Hours (h)
Interval 0.5 to 12.0
|
PRIMARY outcome
Timeframe: Period 3: -0.5, 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 11, 12, 13, 15, 18, 24h post dosePopulation: All randomized participants who received at least one dose of study drug and had evaluable PK data in part B.
Part B: Pharmacokinetics: Area Under the Concentration Versus Time Curve from Zero to 24 Hours Postdose (AUC\[0-24\]) of U-500R.
Outcome measures
| Measure |
100-U Bolus U-500R SC
n=3 Participants
Participants received 100-U of human regular U-500 insulin (U-500R) by subcutaneous (SC) injection.
|
100-U Bolus U-500R CSII
n=5 Participants
Participants received 4.25 U/hour U-500R basal infusion for 12 hours prior to and during the 24 hour clamp plus a 100-U of U-500R via continuous SC insulin infusion (CSII).
|
|---|---|---|
|
Part B: Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to 24 Hours Postdose (AUC[0-24]) of U-500R
|
7790 Picomoles hour per liter (pmol*h/L)
Geometric Coefficient of Variation 57
|
11700 Picomoles hour per liter (pmol*h/L)
Geometric Coefficient of Variation 77
|
PRIMARY outcome
Timeframe: Period 3: -0.5, 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 11, 12, 13, 15, 18, 24h post dosePopulation: All randomized participants who received at least one dose of study drug and had evaluable PK data in part B.
Pharmacokinetics: Maximum Observed Drug Concentration (Cmax) of U-500R.
Outcome measures
| Measure |
100-U Bolus U-500R SC
n=4 Participants
Participants received 100-U of human regular U-500 insulin (U-500R) by subcutaneous (SC) injection.
|
100-U Bolus U-500R CSII
n=5 Participants
Participants received 4.25 U/hour U-500R basal infusion for 12 hours prior to and during the 24 hour clamp plus a 100-U of U-500R via continuous SC insulin infusion (CSII).
|
|---|---|---|
|
Part B: Pharmacokinetics: Maximum Observed Drug Concentration (Cmax) of U-500R
|
699 Pico mole per liter (Pmol/L)
Geometric Coefficient of Variation 47
|
1050 Pico mole per liter (Pmol/L)
Geometric Coefficient of Variation 82
|
PRIMARY outcome
Timeframe: Period 3 day 1: 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 11, 12, 13, 15, 18h post dosePopulation: All randomized participants who received at least one dose of study drug and had evaluable PK data in part B.
Pharmacodynamics: Maximum Glucose Infusion Rate (Rmax) of U-500R.
Outcome measures
| Measure |
100-U Bolus U-500R SC
n=4 Participants
Participants received 100-U of human regular U-500 insulin (U-500R) by subcutaneous (SC) injection.
|
100-U Bolus U-500R CSII
n=5 Participants
Participants received 4.25 U/hour U-500R basal infusion for 12 hours prior to and during the 24 hour clamp plus a 100-U of U-500R via continuous SC insulin infusion (CSII).
|
|---|---|---|
|
Part B: Pharmacodynamics: Maximum Glucose Infusion Rate (Rmax) of U-500R
|
524 Milligram per Minute (mg/min)
Geometric Coefficient of Variation 30
|
588 Milligram per Minute (mg/min)
Geometric Coefficient of Variation 28
|
SECONDARY outcome
Timeframe: Period 1 and 2: -0.5, 0, 0.5, 1, 2, 3, 4, 6, 7, 8, 12, 16, 24h post dosePopulation: All randomized participants who received at least one dose of study drug and had evaluable PK data in Part A.
Part A: Pharmacokinetics: Area Under The Concentration Versus Time Curve From Time Zero to Last Time Point With A Measurable Concentration (AUC\[0-tlast\]) of U-500R.
Outcome measures
| Measure |
100-U Bolus U-500R SC
n=11 Participants
Participants received 100-U of human regular U-500 insulin (U-500R) by subcutaneous (SC) injection.
|
100-U Bolus U-500R CSII
n=11 Participants
Participants received 4.25 U/hour U-500R basal infusion for 12 hours prior to and during the 24 hour clamp plus a 100-U of U-500R via continuous SC insulin infusion (CSII).
|
|---|---|---|
|
Part A: Pharmacokinetics: Area Under The Concentration Versus Time Curve From Time Zero to Last Time Point With A Measurable Concentration (AUC[0-tlast]) of U-500R
|
5230 Picomole hours per liter (pmol^h/L)
Geometric Coefficient of Variation 35
|
6070 Picomole hours per liter (pmol^h/L)
Geometric Coefficient of Variation 70
|
SECONDARY outcome
Timeframe: Period 1 and 2: 0, 0.5, 1, 2, 3, 4, 6, 7, 8, 12, 16, 24h post dosePopulation: All randomized participants who received at least one dose of study drug and had evaluable PD data in Part A.
Part A: Pharmacodynamics (PD): Time to Rmax (tRmax) of U-500R.
Outcome measures
| Measure |
100-U Bolus U-500R SC
n=11 Participants
Participants received 100-U of human regular U-500 insulin (U-500R) by subcutaneous (SC) injection.
|
100-U Bolus U-500R CSII
n=11 Participants
Participants received 4.25 U/hour U-500R basal infusion for 12 hours prior to and during the 24 hour clamp plus a 100-U of U-500R via continuous SC insulin infusion (CSII).
|
|---|---|---|
|
Part A: Pharmacodynamics (PD): Time to Rmax (tRmax) of U-500R
|
8.50 Hour (h)
Geometric Coefficient of Variation 31
|
8.53 Hour (h)
Geometric Coefficient of Variation 35
|
SECONDARY outcome
Timeframe: Period 3: -0.5, 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 11, 12, 13, 15, 18, 24h post dosePopulation: All randomized participants who received at least one dose of study drug and had evaluable PK data in part B.
Part B: Pharmacokinetics: Time to Maximum Concentration (Tmax) of U-500R.
Outcome measures
| Measure |
100-U Bolus U-500R SC
n=4 Participants
Participants received 100-U of human regular U-500 insulin (U-500R) by subcutaneous (SC) injection.
|
100-U Bolus U-500R CSII
n=5 Participants
Participants received 4.25 U/hour U-500R basal infusion for 12 hours prior to and during the 24 hour clamp plus a 100-U of U-500R via continuous SC insulin infusion (CSII).
|
|---|---|---|
|
Part B: Pharmacokinetics: Time to Maximum Concentration (Tmax) of U-500R
|
15 Hours
Interval 5.0 to 18.0
|
15 Hours
Interval 7.0 to 15.0
|
SECONDARY outcome
Timeframe: Period 3: 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 11, 12, 13, 15, 18, 24h post dosePopulation: All randomized participants who received at least one dose of study drug and had evaluable PK data in part B.
Pharmacodynamics: Total Amount of Glucose Infused (Gtot) of U-500R.
Outcome measures
| Measure |
100-U Bolus U-500R SC
n=4 Participants
Participants received 100-U of human regular U-500 insulin (U-500R) by subcutaneous (SC) injection.
|
100-U Bolus U-500R CSII
n=5 Participants
Participants received 4.25 U/hour U-500R basal infusion for 12 hours prior to and during the 24 hour clamp plus a 100-U of U-500R via continuous SC insulin infusion (CSII).
|
|---|---|---|
|
Part B: Pharmacodynamics: Total Amount of Glucose Infused (Gtot) of U-500R
|
441 Grams (g)
Geometric Coefficient of Variation 27
|
510 Grams (g)
Geometric Coefficient of Variation 28
|
SECONDARY outcome
Timeframe: Period 3: 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 11, 12, 13, 15, 18, 24h post dosePopulation: All randomized participants who received at least one dose of study drug and had evaluable PD data in part B.
Part B: Pharmacodynamics: Time to Rmax (tRmax) of U-500R.
Outcome measures
| Measure |
100-U Bolus U-500R SC
n=4 Participants
Participants received 100-U of human regular U-500 insulin (U-500R) by subcutaneous (SC) injection.
|
100-U Bolus U-500R CSII
n=5 Participants
Participants received 4.25 U/hour U-500R basal infusion for 12 hours prior to and during the 24 hour clamp plus a 100-U of U-500R via continuous SC insulin infusion (CSII).
|
|---|---|---|
|
Part B: Pharmacodynamics: Time to Rmax (tRmax) of U-500R
|
12.4 Hours
Geometric Coefficient of Variation 64
|
13.8 Hours
Geometric Coefficient of Variation 7
|
Adverse Events
100-U Bolus U-500R SC
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
100-U Bolus U-500R CSII
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
U-500R BID
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
U-500R TID
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
100-U Bolus U-500R SC
n=11 participants at risk
Participants received 100-U of human regular U-500 insulin (U-500R) by subcutaneous (SC) injection.
|
100-U Bolus U-500R CSII
n=11 participants at risk
Participants received 4.25 U/hour U-500R basal infusion for 12 hours prior to and during the 24 hour clamp plus a 100-U of U-500R via continuous SC insulin infusion (CSII).
|
U-500R BID
n=4 participants at risk
Participants received U-500R twice daily by SC injection for 5 to 10 days.
|
U-500R TID
n=6 participants at risk
Participants received U-500R thrice daily by SC injection for 5 to 10 days.
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
9.1%
1/11 • Number of events 1 • Up to 72 weeks
|
0.00%
0/11 • Up to 72 weeks
|
0.00%
0/4 • Up to 72 weeks
|
0.00%
0/6 • Up to 72 weeks
|
|
Gastrointestinal disorders
Gastrointestinal disorder
|
0.00%
0/11 • Up to 72 weeks
|
9.1%
1/11 • Number of events 1 • Up to 72 weeks
|
0.00%
0/4 • Up to 72 weeks
|
0.00%
0/6 • Up to 72 weeks
|
|
General disorders
Infusion site extravasation
|
0.00%
0/11 • Up to 72 weeks
|
0.00%
0/11 • Up to 72 weeks
|
0.00%
0/4 • Up to 72 weeks
|
16.7%
1/6 • Number of events 1 • Up to 72 weeks
|
|
General disorders
Medical device site swelling
|
0.00%
0/11 • Up to 72 weeks
|
9.1%
1/11 • Number of events 1 • Up to 72 weeks
|
0.00%
0/4 • Up to 72 weeks
|
0.00%
0/6 • Up to 72 weeks
|
|
General disorders
Oedema peripheral
|
0.00%
0/11 • Up to 72 weeks
|
0.00%
0/11 • Up to 72 weeks
|
25.0%
1/4 • Number of events 1 • Up to 72 weeks
|
0.00%
0/6 • Up to 72 weeks
|
|
General disorders
Peripheral swelling
|
9.1%
1/11 • Number of events 1 • Up to 72 weeks
|
0.00%
0/11 • Up to 72 weeks
|
0.00%
0/4 • Up to 72 weeks
|
0.00%
0/6 • Up to 72 weeks
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/11 • Up to 72 weeks
|
0.00%
0/11 • Up to 72 weeks
|
0.00%
0/4 • Up to 72 weeks
|
16.7%
1/6 • Number of events 1 • Up to 72 weeks
|
|
Injury, poisoning and procedural complications
Procedural complication
|
9.1%
1/11 • Number of events 1 • Up to 72 weeks
|
0.00%
0/11 • Up to 72 weeks
|
0.00%
0/4 • Up to 72 weeks
|
0.00%
0/6 • Up to 72 weeks
|
|
Metabolism and nutrition disorders
Increased appetite
|
9.1%
1/11 • Number of events 1 • Up to 72 weeks
|
0.00%
0/11 • Up to 72 weeks
|
0.00%
0/4 • Up to 72 weeks
|
0.00%
0/6 • Up to 72 weeks
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/11 • Up to 72 weeks
|
0.00%
0/11 • Up to 72 weeks
|
25.0%
1/4 • Number of events 1 • Up to 72 weeks
|
0.00%
0/6 • Up to 72 weeks
|
|
Nervous system disorders
Dizziness
|
9.1%
1/11 • Number of events 1 • Up to 72 weeks
|
0.00%
0/11 • Up to 72 weeks
|
0.00%
0/4 • Up to 72 weeks
|
0.00%
0/6 • Up to 72 weeks
|
|
Nervous system disorders
Headache
|
0.00%
0/11 • Up to 72 weeks
|
9.1%
1/11 • Number of events 1 • Up to 72 weeks
|
0.00%
0/4 • Up to 72 weeks
|
0.00%
0/6 • Up to 72 weeks
|
|
Reproductive system and breast disorders
Priapism
|
0.00%
0/11 • Up to 72 weeks
|
9.1%
1/11 • Number of events 1 • Up to 72 weeks
|
0.00%
0/4 • Up to 72 weeks
|
0.00%
0/6 • Up to 72 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/11 • Up to 72 weeks
|
0.00%
0/11 • Up to 72 weeks
|
25.0%
1/4 • Number of events 1 • Up to 72 weeks
|
0.00%
0/6 • Up to 72 weeks
|
|
Skin and subcutaneous tissue disorders
Petechiae
|
0.00%
0/11 • Up to 72 weeks
|
9.1%
1/11 • Number of events 1 • Up to 72 weeks
|
0.00%
0/4 • Up to 72 weeks
|
0.00%
0/6 • Up to 72 weeks
|
|
Surgical and medical procedures
Eye laser surgery
|
9.1%
1/11 • Number of events 1 • Up to 72 weeks
|
0.00%
0/11 • Up to 72 weeks
|
0.00%
0/4 • Up to 72 weeks
|
0.00%
0/6 • Up to 72 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The only disclosure restriction on PI is that sponsor can review results communications and comment 30 days prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. If PI is unwilling to delay the results communication then PI can remove the information that sponsor has specified it reasonably believes would jeopardize its intellectual property interests.
- Publication restrictions are in place
Restriction type: OTHER