Effect of LIK066 on Glucose Absorption in Patients With Type 2 Diabetes Mellitus

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01915849
• Collaborator: (none)
• Enrollment: 14
• Location: 1
• Arms: 4
• Duration (Months): 6
• Patients Per Site Per Month: 2.3

Study Details

Study Description

Brief Summary

The purpose of the study was to assess the effect of LIK066 on intestinal glucose absorption immediately after a single dose (immediate effect) and 6 hours following the dose (after multiple daily doses; sustained effect) in patients with type 2 diabetes mellitus (T2DM).

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Mellitus	Drug: LIK066; Drug: Placebo	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 14 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Official Title: A Randomized, Double-blinded, Placebo-controlled, Crossover Trial to Assess the Effect of Orally Administered LIK066 on Glucose Absorption in Patients With Type 2 Diabetes Mellitus
• Study Start Date: Jul 1, 2013
• Actual Primary Completion Date: Jan 1, 2014
• Actual Study Completion Date: Jan 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: LIK066; LIK066 15 mg, 50 mg and 150 mg; Drug: Placebo
Experimental: 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.	Drug: LIK066; LIK066 15 mg, 50 mg and 150 mg; Drug: Placebo
Experimental: 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.	Drug: LIK066; LIK066 15 mg, 50 mg and 150 mg; Drug: Placebo
Experimental: Sequence 3: 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.	Drug: LIK066; LIK066 15 mg, 50 mg and 150 mg; Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. Area Under the Postprandial Curve (AUC) for Rate of Appearance (Ra) of Exogenous Glucose [Day 1 and Day 4 (pre-meal, every half hour till 5 hour on Day 1 and Day 4)]

   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.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients, age 18-65 years, must have been diagnosed with T2DM at least 6 months prior to screening with HbA1c 6.5 to 10.0%, inclusive, at screening.

• Fasting plasma glucose ≤250mg/dL at screening.

• If treated with metformin, patients must be on a stable dose for 12 weeks prior to randomization and maintain the dose until the end of the study.

Exclusion Criteria:

• Patients with type 1 diabetes mellitus.

• Patients with history of acute diabetic complications within the 6 months prior to screening.

• Pregnant or nursing (lactating) women.

• Women of child-bearing potential unless they are using effective methods of contraception during dosing of study treatment.

• Patients with signs or symptoms of significant diabetic complications.

• Patients treated with certain blood pressure or lipid lowering medications unless patients have been on stable doses for the 12 weeks prior to dosing.

• History of drug or alcohol abuse within the 12 months prior to dosing.

• Any surgical or medical condition, acute or unstable chronic disease which may, based on the investigator's opinion, jeopardize the patient in case of participation in the study.

Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Chula Vista	California	United States	91910

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01915849
• Other Study ID Numbers: CLIK066A2201
• First Posted: Aug 5, 2013
• Last Update Posted: Feb 6, 2015
• Last Verified: Jan 1, 2015

• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Licogliflozin

Study Results

Participant Flow

Arm/Group Title	Sequence 1: LIK066 15 mg/Placebo/LIK066 50 mg/LIK066 150 mg	Sequence 2: LIK066 50 mg/LIK066 15 mg/LIK066 150 mg/Placebo	Sequence 3: LIK066 150 mg/LIK066 50 mg/Placebo/LIK066 15 mg	Sequence 4: Placebo/LIK066 150 mg/LIK066 15 mg/LIK066 50 mg
Arm/Group Description	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.	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.	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.	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.
Period Title: Treatment Period 1 (4 Days)
STARTED	5	3	3	3
COMPLETED	3	3	3	3
NOT COMPLETED	2	0	0	0
Period Title: Treatment Period 1 (4 Days)
STARTED	3	3	3	3
COMPLETED	3	3	3	3
NOT COMPLETED	0	0	0	0
Period Title: Treatment Period 1 (4 Days)
STARTED	3	3	3	3
COMPLETED	3	3	3	3
NOT COMPLETED	0	0	0	0
Period Title: Treatment Period 1 (4 Days)
STARTED	3	3	3	3
COMPLETED	3	3	3	3
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Sequence 1: LIK066 15 mg/Placebo/LIK066 50 mg/LIK066 150 mg	Sequence 2: LIK066 50 mg/LIK066 15 mg/LIK066 150 mg/Placebo	Sequence 3: LIK066 150 mg/LIK066 50 mg/Placebo/LIK066 15 mg	Sequence 4: Placebo/LIK066 150 mg/LIK066 15 mg/LIK066 50 mg	Total
Arm/Group Description	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.	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.	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.	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 of all reporting groups
Overall Participants	5	3	3	3	14
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	53.4 (9.29)	54.0 (10.54)	62.3 (3.06)	56.0 (8.19)	56.0 (8.26)
Sex: Female, Male (Count of Participants)
Female	3 60%	1 33.3%	2 66.7%	1 33.3%	7 50%
Male	2 40%	2 66.7%	1 33.3%	2 66.7%	7 50%

Outcome Measures

1. Primary Outcome

Title	Area Under the Postprandial Curve (AUC) for Rate of Appearance (Ra) of Exogenous Glucose
Description	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.
Time Frame	Day 1 and Day 4 (pre-meal, every half hour till 5 hour on Day 1 and Day 4)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	LIK066 15 mg	LIK066 50 mg	LIK066 150 mg	Placebo
Arm/Group Description	All patients who have received LIK066 15 mg once daily for 4 days.	All patients who have received LIK066 50 mg once daily for 4 days.	All patients who have received LIK066 150 mg once daily for 4 days.	All patients who have received placebo once daily for 4 days.
Measure Participants	14	12	12	11
Day 1	101.97 (29.348)	93.89 (25.852)	63.84 (22.589)	97.76 (30.615)
Day 4	109.99 (27.144)	117.81 (30.881)	112.45 (31.129)	103.97 (23.335)

Adverse Events

Adverse Event Reporting Description	Safety analysis set: all patients that received study drug and with no protocol deviations with relevant impact on safety.
Arm/Group Title	Placebo		LIK066 15 mg		LIK066 50 mg		LIK066 150 mg
Arm/Group Description	Placebo		LIK066 15 mg		LIK066 50 mg		LIK066 150 mg
All Cause Mortality
	Placebo		LIK066 15 mg		LIK066 50 mg		LIK066 150 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		LIK066 15 mg		LIK066 50 mg		LIK066 150 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/14 (0%)		0/12 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		LIK066 15 mg		LIK066 50 mg		LIK066 150 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/12 (41.7%)		8/14 (57.1%)		7/12 (58.3%)		11/12 (91.7%)
Blood and lymphatic system disorders
Anaemia	1/12 (8.3%)		0/14 (0%)		1/12 (8.3%)		0/12 (0%)
Eye disorders
Vision blurred	1/12 (8.3%)		0/14 (0%)		0/12 (0%)		0/12 (0%)
Gastrointestinal disorders
Abdominal pain	0/12 (0%)		0/14 (0%)		0/12 (0%)		1/12 (8.3%)
Diarrhoea	0/12 (0%)		0/14 (0%)		2/12 (16.7%)		8/12 (66.7%)
Flatulence	0/12 (0%)		0/14 (0%)		1/12 (8.3%)		1/12 (8.3%)
Nausea	1/12 (8.3%)		2/14 (14.3%)		2/12 (16.7%)		4/12 (33.3%)
Vomiting	1/12 (8.3%)		0/14 (0%)		1/12 (8.3%)		1/12 (8.3%)
General disorders
Cyst	0/12 (0%)		0/14 (0%)		1/12 (8.3%)		0/12 (0%)
Fatigue	0/12 (0%)		0/14 (0%)		0/12 (0%)		1/12 (8.3%)
Implant site haemorrhage	1/12 (8.3%)		0/14 (0%)		0/12 (0%)		0/12 (0%)
Non-cardiac chest pain	0/12 (0%)		0/14 (0%)		1/12 (8.3%)		0/12 (0%)
Infections and infestations
Rash pustular	0/12 (0%)		1/14 (7.1%)		0/12 (0%)		0/12 (0%)
Upper respiratory tract infection	0/12 (0%)		0/14 (0%)		1/12 (8.3%)		0/12 (0%)
Vulvovaginitis	0/12 (0%)		0/14 (0%)		1/12 (8.3%)		0/12 (0%)
Injury, poisoning and procedural complications
Incision site erythema	0/12 (0%)		0/14 (0%)		1/12 (8.3%)		0/12 (0%)
Metabolism and nutrition disorders
Hypoglycaemia	2/12 (16.7%)		3/14 (21.4%)		2/12 (16.7%)		0/12 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/12 (0%)		1/14 (7.1%)		0/12 (0%)		0/12 (0%)
Nervous system disorders
Headache	0/12 (0%)		1/14 (7.1%)		0/12 (0%)		0/12 (0%)
Tremor	0/12 (0%)		1/14 (7.1%)		0/12 (0%)		0/12 (0%)
Reproductive system and breast disorders
Vulvovaginal pruritus	0/12 (0%)		1/14 (7.1%)		0/12 (0%)		0/12 (0%)
Skin and subcutaneous tissue disorders
Dermatitis contact	0/12 (0%)		1/14 (7.1%)		0/12 (0%)		0/12 (0%)
Ecchymosis	0/12 (0%)		2/14 (14.3%)		0/12 (0%)		2/12 (16.7%)
Erythema	1/12 (8.3%)		0/14 (0%)		2/12 (16.7%)		1/12 (8.3%)
Pruritus	1/12 (8.3%)		0/14 (0%)		1/12 (8.3%)		0/12 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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.