Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
LIK066 · 9 trials · 8 indications
The dose-response relationship of LIK066 as measured by percent change from baseline in body weight relative to placebo after 12 weeks of treatment.
Alanine aminotransferase (ALT) is an enzyme found primarily in the liver. ALT is increased with liver damage. In this study, the blood levels of ALT was used to detect liver injury. Baseline is defined as the mean of measurements taken at the Screening and Baseline visits.
Episodes of diarrhea is defined as the total number of stools with a Bristol Stool Chart (BSC) Score of 6 or 7 on day 3 of each treatment period. BSC is frequently used as a measure of consistency, and a score of 6 or 7 (pourable or watery stool) is considered abnormal.
Dose-response relationship of two dose regimens of LIK066 as measured by the percent change from baseline in body weight relative to placebo after 24 weeks of treatment
Urine was collected over 24 h to measure Urinary Glucose Excretion (UGE) at baseline (Day -1), following a single dose (Day 1) and at the end of the 7-day treatment (Day 7) to assess the effect of a 7 day treatment with LIK066 in subjects with decreased renal function compared to those with normal renal function.
Plasma PK samples were collected at Day 1 and Day 7 and assayed for LIK066 concentrations using validated liquid chromatography-tandem mass spectrometry assays (LC MS/MS). The method will have an LLOQ of at least 5 ng/mL for LIK066. Concentrations were expressed in mass per volume units and refered to LIK066 plasma concentrations. Cmax was determined using the actual recorded sampling times and non-compartmental method(s) to assess the effect of a 7 day treatment with LIK066 in subjects with decreased renal function compared to those with normal renal function. Only descriptive analysis done.
Plasma PK samples were collected at Day 1 and Day 7 and assayed for LIK066 concentrations using validated liquid chromatography-tandem mass spectrometry assays (LC MS/MS). The method will have an LLOQ of at least 5 ng/mL for LIK066. Concentrations were expressed in mass per volume units and refered to LIK066 plasma concentrations. Tmax was determined using the actual recorded sampling times and non-compartmental method(s) to assess the effect of a 7 day treatment with LIK066 in subjects with decreased renal function compared to those with normal renal function. Only descriptive analysis done.
Plasma PK samples were collected at Day 1 and Day 7 and assayed for LIK066 concentrations using validated liquid chromatography-tandem mass spectrometry assays (LC MS/MS). The method will have an LLOQ of at least 5 ng/mL for LIK066. Concentrations were expressed in mass per volume units and refered to LIK066 plasma concentrations. AUCtau was determined using the actual recorded sampling times and non-compartmental method(s) to assess the effect of a 7 day treatment with LIK066 in subjects with decreased renal function compared to those with normal renal function. Only descriptive analysis done.
Plasma PK samples were collected at Day 1 and Day 7 and assayed for LIK066 concentrations using validated liquid chromatography-tandem mass spectrometry assays (LC MS/MS). The method will have an LLOQ of at least 5 ng/mL for LIK066. Concentrations were expressed in mass per volume units and refered to LIK066 plasma concentrations. AUClast was determined using the actual recorded sampling times and non-compartmental method(s) to assess the effect of a 7 day treatment with LIK066 in subjects with decreased renal function compared to those with normal renal function. AUClast is similar to AUCtau on Day 1 since the Tlast for Day 1 = 24hrs (tau = 24hrs); therefore AUClast is not reported for Day1, it is however reported for Day 7 since the Tlast is different from 24 hours. Only descriptive analysis done.
Plasma PK samples were collected at Day 1 and Day 7 and assayed for LIK066 concentrations using validated liquid chromatography-tandem mass spectrometry assays (LC MS/MS). The method will have an LLOQ of at least 5 ng/mL for LIK066. Concentrations were expressed in mass per volume units and refered to LIK066 plasma concentrations. AUCinf was determined using the actual recorded sampling times and non-compartmental method(s) to assess the effect of a 7 day treatment with LIK066 in subjects with decreased renal function compared to those with normal renal function. AUCinf is a single dose parameter and therefore is presented on Day 1 only, after the first dose of LIK066. Only descriptive analysis done.
Plasma PK samples were collected at Day 1 and Day 7 and assayed for LIK066 concentrations using validated liquid chromatography-tandem mass spectrometry assays (LC MS/MS). The method will have an LLOQ of at least 5 ng/mL for LIK066. Concentrations were expressed in mass per volume units and refered to LIK066 plasma concentrations. T1/2 was determined using the actual recorded sampling times and non-compartmental method(s) to assess the effect of a 7 day treatment with LIK066 in subjects with decreased renal function compared to those with normal renal function. T1/2 is only reported at Day 7 only, since there was sampling out to \~5 half-lives after the Day 7 dose of LIK066. Only descriptive analysis done.
Plasma PK samples were collected at Day 1 and Day 7 and assayed for LIK066 concentrations using validated liquid chromatography-tandem mass spectrometry assays (LC MS/MS). The method will have an LLOQ of at least 5 ng/mL for LIK066. Concentrations were expressed in mass per volume units and refered to LIK066 plasma concentrations. CL/F was determined using the actual recorded sampling times and non-compartmental method(s) to assess the effect of a 7 day treatment with LIK066 in subjects with decreased renal function compared to those with normal renal function. Since Day 7 represented steady state of LIK066 in the study, the appropriately calculated steady-state clearance parameter computed was CLss/F and was presented. Only descriptive analysis done.
Plasma PK samples were collected at Day 1 and Day 7 and assayed for LIK066 concentrations using validated liquid chromatography-tandem mass spectrometry assays (LC MS/MS). The method will have an LLOQ of at least 5 ng/mL for LIK066. Concentrations were expressed in mass per volume units and refered to LIK066 plasma concentrations. Vz/F was determined using the actual recorded sampling times and non-compartmental method(s) to assess the effect of a 7 day treatment with LIK066 in subjects with decreased renal function compared to those with normal renal function. Only descriptive analysis done.
Urine PK samples were collected at Day 1 and Day 7 and assayed for LIK066 concentrations using validated liquid chromatography-tandem mass spectrometry assays (LC MS/MS). The method will have an LLOQ of at least 5 ng/mL for LIK066. Concentrations were expressed in mass per volume units and refered to LIK066 plasma concentrations. CLr was determined using the actual recorded sampling times and non-compartmental method(s) to assess the effect of a 7 day treatment with LIK066 in subjects with decreased renal function compared to those with normal renal function. Only descriptive analysis done.
Triplicate body weight measurements at each visit were averaged and represented body weight at that visit. Baseline was defined to be the body weight at the last visit prior to the first treatment. Baseline is Day -1 in Part 1. Percent change is calculated as \[(post baseline- Baseline) /Baseline\] \* 100. A longitudinal mixed effects model for percent change in body weight was used. The model included fixed effects of treatment, time, glycemic status (a stratification factor for randomization), the treatment-by- time interaction, the treatment-by-glycemic status interaction, the time-by-glycemic status interaction, and the treatment-by-time-by-glycemic status interaction, and Baseline body weight as a covariate.
This endpoint reports patients with at least one AE (any AE), serious AE and death.
Triplicate body weight measurements at each visit were averaged and represented body weight at that visit. Baseline was defined to be the body weight at the last visit prior to the first treatment. Part 1: Baseline is defined as Day -1. Part 2: Baseline is defined as Day 1 predose. Percent change is calculated as \[(post baseline- Baseline) /Baseline\] \* 100. A longitudinal mixed effects model for percent change in body weight was used. The longitudinal mixed effects model included fixed effects of treatment, time, glycemic status (a stratification factor for randomization), the treatment-by-time interaction, the treatment-by-glycemic status interaction, the time-by-glycemic status interaction, the treatment-by-time-by-glycemic status interaction, a random effect for study part and baseline body weight as a covariate.
This endpoint reports patients with at least one AE (any AE), serious AE and death
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.
| Arm | Type | Description |
|---|---|---|
| LIK066 2.5 mg | EXPERIMENTAL | Eligible patients randomized to this arm will receive LIK066 2.5 mg orally daily for 12 weeks. |
| LIK066 10 mg | EXPERIMENTAL | Eligible patients randomized to this arm will receive LIK066 10 mg orally daily for 12 weeks. |
| LIK066 25 mg | EXPERIMENTAL | Eligible patients randomized to this arm will receive LIK066 25 mg orally daily for 12 weeks. |
| LIK066 50 mg | EXPERIMENTAL | Eligible patients randomized to this arm will receive LIK066 50 mg orally daily for 12 weeks. |
| Placebo | PLACEBO_COMPARATOR | Eligible patient randomized to this arm will receive LIK066 matching placebo orally daily for 12 weeks. |
| LIK066 30 mg | EXPERIMENTAL | Film coated tablet of LIK066 30 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84. |
| LIK066 150 mg | EXPERIMENTAL | Film coated tablet of LIK066 150 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84 |
| LIK066 | EXPERIMENTAL | LIK066 tablets received three times daily; before breakfast, lunch and dinner for 14 days and once on day 15 morning before meal test |
| Part A: LIK066 + P1: 50% CHO / P2: 25% CHO / P3: 0% CHO | EXPERIMENTAL | Period 1 (Day 1-3): Daily dose of 50 mg LIK066 + 50% carbohydrate (CHO) Period 2 (Day 9-11): Daily dose of 50 mg LIK066 + 25% carbohydrate Period 3 (Day 17-19): Daily dose of 50 mg LIK066 + 0% carbohydrate |
| Part A: LIK066 + P1: 25% CHO / P2: 0% CHO / P3: 50% CHO | EXPERIMENTAL | Period 1 (Day 1-3): Daily dose of 50 mg LIK066 + 25% carbohydrate (CHO) Period 2 (Day 9-11): Daily dose of 50 mg LIK066 + 0% carbohydrate Period 3 (Day 17-19): Daily dose of 50 mg LIK066 + 50% carbohydrate |
| Part A: LIK066 + P1: 0% CHO / P2: 50% CHO / P3: 25% CHO | EXPERIMENTAL | Period 1 (Day 1-3): Daily dose of 50 mg LIK066 + 0% carbohydrate (CHO) Period 2 (Day 9-11): Daily dose of 50 mg LIK066 + 50% carbohydrate Period 3 (Day 17-19): Daily dose of 50 mg LIK066 + 25% carbohydrate |
| Part A: LIK066 + P1: 8% CHO | EXPERIMENTAL | Period 1 (Day 1-3): Daily dose of 50 mg LIK066 + 8% carbohydrate (CHO) PROTOCOL DEVIATION: subjects received 8% CHO in error and were discontinued after Period 1. |
| Part B: LIK066 + 50% CHO + P1: NS / P2: PS / P3: CC | EXPERIMENTAL | Period 1 (Day 1-3): Daily dose of 50 mg LIK066+50% carbohydrate + no supplement (NS) Period 2 (Day 9-11): Daily dose of 50 mg LIK066+50% carbohydrate + 6 g psyllium (PS) Period 3 (Day 17-19): Daily dose of 50 mg LIK066+50% carbohydrate +1g calcium carbonate (CC) |
| Part B: LIK066 + 50% CHO + P1: PS / P2: CC / P3: NS | EXPERIMENTAL | Period 1 (Day 1-3): Daily dose of 50 mg LIK066+50% carbohydrate + 6 g psyllium (PS) Period 2 (Day 9-11): Daily dose of 50 mg LIK066+50% carbohydrate +1g calcium carbonate (CC) Period 3 (Day 17-19): Daily dose of 50 mg LIK066+50% carbohydrate + no supplement (NS) |
| Part B: LIK066 + 50% CHO + P1: CC / P2: NS / P3: PS | EXPERIMENTAL | Period 1 (Day 1-3): Daily dose of 50 mg LIK066+50% carbohydrate +1g calcium carbonate (CC) Period 2 (Day 9-11): Daily dose of 50 mg LIK066+50% carbohydrate + no supplement (NS) Period 3 (Day 17-19): Daily dose of 50 mg LIK066+50% carbohydrate + 6 g psyllium (PS) |
| LIK066 2.5mg qd (Epoch 3) | EXPERIMENTAL | LIK066 2.5mg qd (once daily) dosing frequency for 24 weeks. |
| Placebo (Epoch 3) | PLACEBO_COMPARATOR | Matching placebo tablets for 24 weeks |
| LIK066 10mg qd (Epoch 3) | EXPERIMENTAL | LIK066 10mg qd (once daily) dosing frequency for 24 weeks |
| LIK066 50mg qd (Epoch 3) | EXPERIMENTAL | LIK066 50mg qd (once daily) dosing frequency for 24 weeks |
| LIK066 150mg qd (Epoch 3) | EXPERIMENTAL | LIK066 150mg qd (once daily) dosing frequency for 24 weeks |
| LIK066 2.5mg bid (Epoch 3) | EXPERIMENTAL | LIK066 2.5mg bid (once daily) dosing frequency for 24 weeks |
| LIK066 5mg bid (Epoch 3) | EXPERIMENTAL | LIK066 5mg bid (once daily) dosing frequency for 24 weeks |
| LIK066 25mg bid (Epoch 3) | EXPERIMENTAL | LIK066 25mg bid (once daily) dosing frequency for 24 weeks |
| LIK066 50mg bid (Epoch 3) | EXPERIMENTAL | LIK066 50mg bid dosing frequency for 24 weeks |
| LIK066 qd/LIK066 25mg qd (Epoch 4) | EXPERIMENTAL | Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily |
| LIK066 bid/LIK066 35mg qd (Epoch 4) | EXPERIMENTAL | Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily |
| Placebo/LIK066 25mg qd (Epoch 4) | EXPERIMENTAL | Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily |
| Placebo/Placebo (Epoch 4) | PLACEBO_COMPARATOR | Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily |
| Mild | EXPERIMENTAL | Patients with mild renal impairment (Group 1) received LIK066 50 mg qd before breakfast for 7 days. |
| Moderate A | EXPERIMENTAL | Patients with moderate renal impairment grade A (Group 2) received LIK066 50 mg qd before breakfast for 7 days. |
| Moderate B | EXPERIMENTAL | Patients with moderate renal impairment grade B (Group 3) received LIK066 50 mg qd before breakfast for 7 days. |
| Severe | EXPERIMENTAL | Patients with severe renal impairment (Group 4) received LIK066 50 mg qd before breakfast for 7 days. |
| Normal | EXPERIMENTAL | Patients with normal renal function (Group 5) received LIK066 50 mg qd before breakfast for 7 days. |
| Part 1: LIK066 150 mg once daily (qd) | EXPERIMENTAL | LIK066 150 mg qd within 15 minutes before starting lunch |
| Part 1: Placebo once daily | PLACEBO_COMPARATOR | Matching placebo tablets of LCZ696 150 mg within 15 minutes before starting lunch. |
| Part 2: LIK066 75 mg twice daily (bid) | EXPERIMENTAL | LIK066 75 mg bid before breakfast and dinner |
| Part 2: LIK066 50 mg three times daily (tid) | EXPERIMENTAL | LIK066 50 mg tid before all 3 meals; |
| Part 2: Placebo three times daily | PLACEBO_COMPARATOR | Matching placebo tablets tid before meals. |
| Sequence 1: LIK066 15 mg/Placebo/LIK066 50 mg/LIK066 150 mg | EXPERIMENTAL | 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 | EXPERIMENTAL | 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 | EXPERIMENTAL | 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 3: Placebo/LIK066 150 mg/LIK066 15 mg/LIK066 50 mg | EXPERIMENTAL | 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. |
| LIK066 in healthy subjects | EXPERIMENTAL | - |
| Matching placebo in healthy subjects | PLACEBO_COMPARATOR | - |
| LIK066 in patients with type 2 diabetes mellitus | EXPERIMENTAL | - |
| Matching placebo in patients with type 2 diabetes mellitus | PLACEBO_COMPARATOR | - |
| Name | Type | Description |
|---|---|---|
| LIK066 | DRUG | LIK066 will be supplied in different doses as tablets to be taken orally daily. |
| Placebo | DRUG | Placebo will be supplied as tablets to be taken daily orally. |
| Carbohydrate 50% | DIETARY_SUPPLEMENT | 50% carbohydrate in breakfast meal |
| Carbohydrate 25% | DIETARY_SUPPLEMENT | 25% carbohydrate in breakfast meal |
| Carbohydrate 8% | DIETARY_SUPPLEMENT | 8% carbohydrate in breakfast meal |
| Carbohydrate 0% | DIETARY_SUPPLEMENT | 0% carbohydrate in breakfast meal |
| Psyllium | DIETARY_SUPPLEMENT | Powder 6 grams |
| Calcium carbonate | DIETARY_SUPPLEMENT | Liquid 1 gram (4 mL equivalent sugar free) |
Inclusion Criteria: * Patients with obesity disease and inadequately controlled body weight with diet and/or exercise * BMI ≥ 25 kg/m\^2 combined with at least two obesity-related comorbidities, or BMI ≥ 35 kg/m\^2 at least one obesity-related comorbidity * Patients with FPG ≥ 110 mg/dL and/or 5.6%...
LIK066 is an investigational small molecule being developed for metabolic conditions including obesity, elevated body mass index, type 2 diabetes mellitus, and obese patients with non-alcoholic steatohepatitis (NASH). It has also been studied in patients with renal impairment and polycystic ovary syndrome. LIK066 is not approved and remains in clinical development.
LIK066 is being developed by Novartis AG, a pharmaceutical company traded on the New York Stock Exchange under the ticker symbol NVS. The drug is an investigational small molecule in the metabolic therapeutic area.
LIK066 has completed Phase 2 clinical trials. It is an investigational drug and has not been approved by regulatory authorities. All three clinical trials listed for LIK066 are completed, with no active trials currently ongoing.
LIK066 has been studied in three completed clinical trials: NCT01407003, a Phase 1 trial in healthy subjects and patients with type 2 diabetes mellitus; NCT01915849, a Phase 1 trial on glucose absorption in type 2 diabetes patients; and NCT02470403, a Phase 2 trial on body weight in patients with elevated body mass index. A fourth trial, NCT03152591, studied LIK066 in overweight and obese women with polycystic ovary syndrome.
LIK066 is the investigational code name used by Novartis for this small molecule. No alternative brand names or other designations have been disclosed in the clinical trial records.
LIK066 is a small molecule being developed for metabolic conditions. The specific molecular target or mechanism of action has not been disclosed in the available clinical trial information.