Trial Outcomes & Findings for Effect of LIK066 on Glucose Absorption in Patients With Type 2 Diabetes Mellitus (NCT NCT01915849)
NCT ID: NCT01915849
Last Updated: 2015-02-06
Results Overview
Glucose fluxes during a mixed meal were measured using a dual glucose tracer method and non-steady state Steele equations. The rate of appearance of meal (or exogenous) glucose in the blood (also referred to as intestinal glucose absorption or Ra meal) after a mixed meal following LIK066 administration on Days 1 and 4 was the primary PD assessment in this study.The postprandial AUC was calculated using the linear trapezoidal rule. The sample collected at 7 hours after the start of the infusion was treated as the pre-meal, 0 hour measurement for the AUC0-5 hr calculation.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
14 participants
Primary outcome timeframe
Day 1 and Day 4 (pre-meal, every half hour till 5 hour on Day 1 and Day 4)
Results posted on
2015-02-06
Participant Flow
Participant milestones
| Measure |
Sequence 1: LIK066 15 mg/Placebo/LIK066 50 mg/LIK066 150 mg
Period 1- LIK066 15 mg treatment once daily (q.d.) for 4 days. Period 2- Placebo treatment once daily for 4 days. Period 3 - LIK066 50 mg treatment once daily (q.d.) for 4 days. Period 4- LIK066 150 mg treatment once daily (q.d.) for 4 days. 14 days washout periods between treatment periods.
|
Sequence 2: LIK066 50 mg/LIK066 15 mg/LIK066 150 mg/Placebo
Period 1- LIK066 50 mg treatment once daily (q.d.) for 4 days. Period 2- LIK066 15 mg treatment once daily (q.d.) for 4 days. Period 3- LIK066 150 mg treatment once daily (q.d.) for 4 days. Period 4- Placebo treatment once daily for 4 days. 14 days washout periods between treatment periods.
|
Sequence 3: LIK066 150 mg/LIK066 50 mg/Placebo/LIK066 15 mg
Period 1- LIK066 150 mg treatment once daily (q.d.) for 4 days. Period 2- LIK066 50 mg treatment once daily (q.d.) for 4 days. Period 3- Placebo treatment once daily for 4 days. Period 4- LIK066 15 mg treatment once daily (q.d.) for 4 days. 14 days washout periods between treatment periods.
|
Sequence 4: Placebo/LIK066 150 mg/LIK066 15 mg/LIK066 50 mg
Period 1- Placebo treatment once daily (q.d.) for 4 days. Period 2- LIK066 150 mg treatment once daily (q.d.) for 4 days. Period 3- LIK066 15 mg treatment once daily (q.d.) for 4 days. Period 4- LIK066 50 mg treatment once daily (q.d.) for 4 days. 14 days washout periods between treatment periods.
|
|---|---|---|---|---|
|
Treatment Period 1 (4 Days)
STARTED
|
5
|
3
|
3
|
3
|
|
Treatment Period 1 (4 Days)
COMPLETED
|
3
|
3
|
3
|
3
|
|
Treatment Period 1 (4 Days)
NOT COMPLETED
|
2
|
0
|
0
|
0
|
|
Treatment Period 2 (4 Days)
STARTED
|
3
|
3
|
3
|
3
|
|
Treatment Period 2 (4 Days)
COMPLETED
|
3
|
3
|
3
|
3
|
|
Treatment Period 2 (4 Days)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Treatment Period 3 (4 Days)
STARTED
|
3
|
3
|
3
|
3
|
|
Treatment Period 3 (4 Days)
COMPLETED
|
3
|
3
|
3
|
3
|
|
Treatment Period 3 (4 Days)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Treatment Period 4 (4 Days)
STARTED
|
3
|
3
|
3
|
3
|
|
Treatment Period 4 (4 Days)
COMPLETED
|
3
|
3
|
3
|
3
|
|
Treatment Period 4 (4 Days)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Sequence 1: LIK066 15 mg/Placebo/LIK066 50 mg/LIK066 150 mg
Period 1- LIK066 15 mg treatment once daily (q.d.) for 4 days. Period 2- Placebo treatment once daily for 4 days. Period 3 - LIK066 50 mg treatment once daily (q.d.) for 4 days. Period 4- LIK066 150 mg treatment once daily (q.d.) for 4 days. 14 days washout periods between treatment periods.
|
Sequence 2: LIK066 50 mg/LIK066 15 mg/LIK066 150 mg/Placebo
Period 1- LIK066 50 mg treatment once daily (q.d.) for 4 days. Period 2- LIK066 15 mg treatment once daily (q.d.) for 4 days. Period 3- LIK066 150 mg treatment once daily (q.d.) for 4 days. Period 4- Placebo treatment once daily for 4 days. 14 days washout periods between treatment periods.
|
Sequence 3: LIK066 150 mg/LIK066 50 mg/Placebo/LIK066 15 mg
Period 1- LIK066 150 mg treatment once daily (q.d.) for 4 days. Period 2- LIK066 50 mg treatment once daily (q.d.) for 4 days. Period 3- Placebo treatment once daily for 4 days. Period 4- LIK066 15 mg treatment once daily (q.d.) for 4 days. 14 days washout periods between treatment periods.
|
Sequence 4: Placebo/LIK066 150 mg/LIK066 15 mg/LIK066 50 mg
Period 1- Placebo treatment once daily (q.d.) for 4 days. Period 2- LIK066 150 mg treatment once daily (q.d.) for 4 days. Period 3- LIK066 15 mg treatment once daily (q.d.) for 4 days. Period 4- LIK066 50 mg treatment once daily (q.d.) for 4 days. 14 days washout periods between treatment periods.
|
|---|---|---|---|---|
|
Treatment Period 1 (4 Days)
Protocol Violation
|
1
|
0
|
0
|
0
|
|
Treatment Period 1 (4 Days)
Withdrawal by Subject
|
1
|
0
|
0
|
0
|
Baseline Characteristics
Effect of LIK066 on Glucose Absorption in Patients With Type 2 Diabetes Mellitus
Baseline characteristics by cohort
| Measure |
Sequence 1: LIK066 15 mg/Placebo/LIK066 50 mg/LIK066 150 mg
n=5 Participants
Period 1- LIK066 15 mg treatment once daily (q.d.) for 4 days. Period 2- Placebo treatment once daily for 4 days. Period 3 - LIK066 50 mg treatment once daily (q.d.) for 4 days. Period 4- LIK066 150 mg treatment once daily (q.d.) for 4 days. 14 days washout periods between treatment periods.
|
Sequence 2: LIK066 50 mg/LIK066 15 mg/LIK066 150 mg/Placebo
n=3 Participants
Period 1- LIK066 50 mg treatment once daily (q.d.) for 4 days. Period 2- LIK066 15 mg treatment once daily (q.d.) for 4 days. Period 3- LIK066 150 mg treatment once daily (q.d.) for 4 days. Period 4- Placebo treatment once daily for 4 days. 14 days washout periods between treatment periods.
|
Sequence 3: LIK066 150 mg/LIK066 50 mg/Placebo/LIK066 15 mg
n=3 Participants
Period 1- LIK066 150 mg treatment once daily (q.d.) for 4 days. Period 2- LIK066 50 mg treatment once daily (q.d.) for 4 days. Period 3- Placebo treatment once daily for 4 days. Period 4- LIK066 15 mg treatment once daily (q.d.) for 4 days. 14 days washout periods between treatment periods.
|
Sequence 4: Placebo/LIK066 150 mg/LIK066 15 mg/LIK066 50 mg
n=3 Participants
Period 1- Placebo treatment once daily (q.d.) for 4 days. Period 2- LIK066 150 mg treatment once daily (q.d.) for 4 days. Period 3- LIK066 15 mg treatment once daily (q.d.) for 4 days. Period 4- LIK066 50 mg treatment once daily (q.d.) for 4 days. 14 days washout periods between treatment periods.
|
Total
n=14 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
53.4 Years
STANDARD_DEVIATION 9.29 • n=5 Participants
|
54.0 Years
STANDARD_DEVIATION 10.54 • n=7 Participants
|
62.3 Years
STANDARD_DEVIATION 3.06 • n=5 Participants
|
56.0 Years
STANDARD_DEVIATION 8.19 • n=4 Participants
|
56.0 Years
STANDARD_DEVIATION 8.26 • n=21 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
7 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
7 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Day 1 and Day 4 (pre-meal, every half hour till 5 hour on Day 1 and Day 4)Population: The pharmacodynamic (PD) analysis set included all patients with any available PD data, who received any study drug and experienced no protocol deviations with relevant impact on PD data.
Glucose fluxes during a mixed meal were measured using a dual glucose tracer method and non-steady state Steele equations. The rate of appearance of meal (or exogenous) glucose in the blood (also referred to as intestinal glucose absorption or Ra meal) after a mixed meal following LIK066 administration on Days 1 and 4 was the primary PD assessment in this study.The postprandial AUC was calculated using the linear trapezoidal rule. The sample collected at 7 hours after the start of the infusion was treated as the pre-meal, 0 hour measurement for the AUC0-5 hr calculation.
Outcome measures
| Measure |
LIK066 15 mg
n=14 Participants
All patients who have received LIK066 15 mg once daily for 4 days.
|
LIK066 50 mg
n=12 Participants
All patients who have received LIK066 50 mg once daily for 4 days.
|
LIK066 150 mg
n=12 Participants
All patients who have received LIK066 150 mg once daily for 4 days.
|
Placebo
n=11 Participants
All patients who have received placebo once daily for 4 days.
|
|---|---|---|---|---|
|
Area Under the Postprandial Curve (AUC) for Rate of Appearance (Ra) of Exogenous Glucose
Day 4
|
109.99 (umol/kg FFM/min)*hr
Standard Deviation 27.144
|
117.81 (umol/kg FFM/min)*hr
Standard Deviation 30.881
|
112.45 (umol/kg FFM/min)*hr
Standard Deviation 31.129
|
103.97 (umol/kg FFM/min)*hr
Standard Deviation 23.335
|
|
Area Under the Postprandial Curve (AUC) for Rate of Appearance (Ra) of Exogenous Glucose
Day 1
|
101.97 (umol/kg FFM/min)*hr
Standard Deviation 29.348
|
93.89 (umol/kg FFM/min)*hr
Standard Deviation 25.852
|
63.84 (umol/kg FFM/min)*hr
Standard Deviation 22.589
|
97.76 (umol/kg FFM/min)*hr
Standard Deviation 30.615
|
Adverse Events
Placebo
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
LIK066 15 mg
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
LIK066 50 mg
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
LIK066 150 mg
Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo
n=12 participants at risk
Placebo
|
LIK066 15 mg
n=14 participants at risk
LIK066 15 mg
|
LIK066 50 mg
n=12 participants at risk
LIK066 50 mg
|
LIK066 150 mg
n=12 participants at risk
LIK066 150 mg
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
8.3%
1/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
0.00%
0/14
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
8.3%
1/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
0.00%
0/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
|
Eye disorders
Vision blurred
|
8.3%
1/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
0.00%
0/14
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
0.00%
0/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
0.00%
0/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
0.00%
0/14
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
0.00%
0/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
8.3%
1/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
0.00%
0/14
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
16.7%
2/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
66.7%
8/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
0.00%
0/14
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
8.3%
1/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
8.3%
1/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
|
Gastrointestinal disorders
Nausea
|
8.3%
1/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
14.3%
2/14
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
16.7%
2/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
33.3%
4/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
|
Gastrointestinal disorders
Vomiting
|
8.3%
1/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
0.00%
0/14
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
8.3%
1/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
8.3%
1/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
|
General disorders
Cyst
|
0.00%
0/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
0.00%
0/14
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
8.3%
1/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
0.00%
0/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
|
General disorders
Fatigue
|
0.00%
0/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
0.00%
0/14
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
0.00%
0/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
8.3%
1/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
|
General disorders
Implant site haemorrhage
|
8.3%
1/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
0.00%
0/14
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
0.00%
0/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
0.00%
0/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
0.00%
0/14
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
8.3%
1/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
0.00%
0/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
|
Infections and infestations
Rash pustular
|
0.00%
0/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
7.1%
1/14
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
0.00%
0/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
0.00%
0/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
0.00%
0/14
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
8.3%
1/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
0.00%
0/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
|
Infections and infestations
Vulvovaginitis
|
0.00%
0/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
0.00%
0/14
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
8.3%
1/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
0.00%
0/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
|
Injury, poisoning and procedural complications
Incision site erythema
|
0.00%
0/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
0.00%
0/14
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
8.3%
1/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
0.00%
0/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
16.7%
2/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
21.4%
3/14
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
16.7%
2/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
0.00%
0/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
7.1%
1/14
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
0.00%
0/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
0.00%
0/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
|
Nervous system disorders
Headache
|
0.00%
0/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
7.1%
1/14
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
0.00%
0/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
0.00%
0/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
|
Nervous system disorders
Tremor
|
0.00%
0/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
7.1%
1/14
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
0.00%
0/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
0.00%
0/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
|
Reproductive system and breast disorders
Vulvovaginal pruritus
|
0.00%
0/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
7.1%
1/14
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
0.00%
0/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
0.00%
0/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
0.00%
0/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
7.1%
1/14
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
0.00%
0/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
0.00%
0/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
|
Skin and subcutaneous tissue disorders
Ecchymosis
|
0.00%
0/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
14.3%
2/14
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
0.00%
0/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
16.7%
2/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
|
Skin and subcutaneous tissue disorders
Erythema
|
8.3%
1/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
0.00%
0/14
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
16.7%
2/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
8.3%
1/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
8.3%
1/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
0.00%
0/14
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
8.3%
1/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
0.00%
0/12
Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
- Publication restrictions are in place
Restriction type: OTHER