Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Aramchol meglumine, Aramchol free acid, Aramchol free acid, single dose
Aramchol · 11 trials · 11 indications
absolute % change from baseline to end of study in liver triglycerides to water ratio (fat/water+fat) as measured by MRS
Blood samples will be collected for pharmacokinetics characterization. Cmax will be calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.
Blood samples will be collected for pharmacokinetics characterization. Tmax will be calculated from plasma concentration-time data using non-compartmental methods based on the actual time of sample collection and summarized using descriptive statistics
Blood samples will be collected for pharmacokinetics characterization. AUC of Aramchol will be calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.
Observed maximal concentration after administration
Area under the concentration/time curve to the last measurable concentration, calculated by the trapezoidal rule from time 0 h to last observed concentration at time t
Area under the concentration/time curve, from time 0 h extrapolated to infinity
Measure the AUC(0-inf) of orally and intravenously (IV) administered Aramchol
Assess the mass balance recovery of total amounts of radioactivity excreted in urine and feces
Assess the potential metabolites of Aramchol and determine their chemical structure in plasma, urine and fecal samples
AUC from time 0 to the dosing interval tau measured at steady state. Blood was collected at the following time points: before dosing (0 hour) and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 18, 24, 48, 72, 96, 120, 144, 168, 192, and 240 hours
Maximum plasma concentrations (Cmax,ss) Blood was collected at the following time points: before dosing (0 hour) and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 18, 24, 48, 72, 96, 120, 144, 168, 192, and 240 hours
CL/F measured after single dose in Part 1 Blood was collected at the following time points: before dosing (0 hour) and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 18, 24, 48, 72, 96, 120, 144, 168, 192, and 240 hours
AUC
Cavg
Ctau
Maximum plasma concentration
Maximum plasma concentration
Time of maximum plasma concentration
Time of maximum plasma concentration
Percentage of AUC that was extrapolated
Percentage of AUC that was extrapolated
Terminal elimination half-life
Terminal elimination half-life
Clearance/fraction of dose absorbed
Clearance/fraction of dose absorbed
Volume of distribution/fraction of dose absorbed
Volume of distribution/fraction of dose absorbed
Mean residence time
Mean residence time
Terminal rate constant
Terminal rate constant
| Arm | Type | Description |
|---|---|---|
| Aramchol 600mg | EXPERIMENTAL | One tablet of Aramchol 400 mg and one tablet of Aramchol 200 mg. |
| Aramchol 400mg | EXPERIMENTAL | One tablet of Aramchol 400 mg and one tablet of matching placebo for Aramchol. |
| Placebo | PLACEBO_COMPARATOR | Two tablet of Aramchol matching placebo. |
| high dose | EXPERIMENTAL | Aramchol 300 mg daily (high dose) |
| low dose | EXPERIMENTAL | 100 mg daily (low dose) |
| Part A- Administration of Aramchol Meglumine tablet | EXPERIMENTAL | 12 subjects will be randomized to Part A. Participants will receive Aramchol meglumine tablet (test formulation) at 2 different single doses and plasma concentration will be assessed. |
| Part B- Administration of Aramchol meglumine or Aramchol acid tablets | EXPERIMENTAL | 20 subjects will be randomized to Part B. Participants will receive Aramchol meglumine once daily for 10 days based on a dose predicted in Part A. Steady-state plasma concentration of Aramchol will be assessed. |
| Subjects receiving a single 400 mg dose of Aramchol meglumine in Period 1 | EXPERIMENTAL | A single 400 mg dose of Aramchol meglumine will be administered to all study subjects in Period 1. |
| Subjects receiving a second dose of Aramchol meglumine or Aramchol free acid in Period 2 | ACTIVE_COMPARATOR | In Period 2, study subjects will be randomized 1:1 to receive Aramchol meglumine or 300 mg tablet of Aramchol free acid (Reference) |
| Subjects receiving a second dose of Aramchol meglumine or Aramchol free acid in Period 3 | ACTIVE_COMPARATOR | In Period 3, study subjects will be randomized 1:1 to receive Aramchol meglumine or 300 mg tablet of Aramchol free acid (Reference) |
| Single dose administration of Aramchol in Part 1 and Part 2 | EXPERIMENTAL | 6 subjects received Aramchol in Part 1 and Part 2 of the study |
| Part 1: Mild Hepatic Impairment (Cohort A) | EXPERIMENTAL | 8 mild hepatic impaired subjects |
| Part 1: Moderate Hepatic Impairment (Cohort B) | EXPERIMENTAL | 8 moderate hepatic impaired subjects |
| Part 1: Severe Hepatic Impairment (Cohort C) | EXPERIMENTAL | 8 severe hepatic impaired subjects |
| Part 1: Healthy Volunteers (Cohort D) | EXPERIMENTAL | 15 matched healthy volunteers |
| Part 2: Mild Hepatic Impairment Cohort | EXPERIMENTAL | 4 mild hepatic impaired subjects |
| Part 2: Moderate Hepatic Impairment Cohort | EXPERIMENTAL | 7 moderate hepatic impaired subjects |
| Part 2: Healthy Volunteers Cohort | EXPERIMENTAL | 7 matched healthy volunteers |
| Aramchol 300 mg | EXPERIMENTAL | Aramchol 300 mg twice daily (every 12 hours) |
| Aramchol 600 mg | EXPERIMENTAL | Aramchol 600 mg once daily (every 24 hours) |
| Midazolam, Atorvastatin / Aramchol, Midazolam, Atorvastatin | OTHER | Midazolam 2 mg -atorvastatin 40 mg /Aramchol 600mg -midazolam 2 mg-atorvastatin 40 mg (MA/MAA) |
| Part A- Single Dose- 400 mg Aramchol | ACTIVE_COMPARATOR | Part A: Subjects will receive a single dose of 400 mg Aramchol, 600 mg Aramchol or placebo. |
| Part A- Single Dose- 600 mg Aramchol | ACTIVE_COMPARATOR | Part A: Subjects will receive a single dose of 400 mg Aramchol, 600 mg Aramchol or placebo. |
| Part A-Single Dose-Placebo | PLACEBO_COMPARATOR | Part A: Subjects will receive a single dose of 400 mg Aramchol, 600 mg Aramchol or placebo. |
| Part B-Multiple Dose-400 mg Aramchol | ACTIVE_COMPARATOR | Part B: Subjects will receive multiple doses of 400 mg Aramchol, 600 mg Aramchol or placebo tablets for 10 consecutive days. |
| Part B-Multiple Dose-600 mg Aramchol | ACTIVE_COMPARATOR | Part B: Subjects will receive multiple doses of 400 mg Aramchol, 600 mg Aramchol or placebo tablets for 10 consecutive days. |
| Part B-Multiple Dose-Placebo | PLACEBO_COMPARATOR | Part B: Subjects will receive multiple doses of 400 mg Aramchol, 600 mg Aramchol or placebo tablets for 10 consecutive days. |
| PART A (single dose)-200 mg | ACTIVE_COMPARATOR | 200 mg ARAMCHOL |
| PART A (single dose)-400 mg | ACTIVE_COMPARATOR | 400 mg ARAMCHOL |
| Part B ( food effect)- -Fasting | ACTIVE_COMPARATOR | 600 mg Aramchol tablets under fasting conditions (fasting for at least 10 hours before and 4 hours after dosing) |
| Part B ( food effect)- -Fed | ACTIVE_COMPARATOR | 600 mg Aramchol tablets under fed conditions (fasting for at least 10 hours before dosing, consumption of a high calorie high fat meal within 30 minutes prior to drug administration and no food for additional 4 hours after dosing) |
| Part C ( multiple doses)- 200 mg | ACTIVE_COMPARATOR | 200 mg Aramchol tablets for ten consecutive days. |
| Part C ( multiple doses)- 400 mg | ACTIVE_COMPARATOR | 400 mg Aramchol tablets for ten consecutive days. |
| Part C ( multiple doses)- 600 mg | ACTIVE_COMPARATOR | 600 mg Aramchol tablets for ten consecutive days. |
| Part C ( multiple doses)- Placebo | PLACEBO_COMPARATOR | Placebo tablets for ten consecutive days. |
| Dose 1 | EXPERIMENTAL | Dose 30 mg |
| Dose 2 | EXPERIMENTAL | Dose 100 mg |
| Dose 3 | EXPERIMENTAL | Dose 300 mg |
| Dose 4 | EXPERIMENTAL | Dose 900 mg |
| Dose 1 repeated | EXPERIMENTAL | Dose 30 mg for 4 days |
| Dose 2 repeated | EXPERIMENTAL | Dose high for 4 days |
| Name | Type | Description |
|---|---|---|
| Aramchol | DRUG | Subjects will be administered Aramchol as follows: * One tablet of Aramchol 400 mg and one tablet of matching placebo for Aramchol. * One tablet of Aramchol 400 mg and one tablet of Aramchol 200 mg. * Two tablet of Aramchol matching placebo. The tablets should be taken orally in the morning within 30 min after breakfast with a glass of water (250 ml). Subjects are allowed to omit study drugs up to 3 consecutive days during the study. |
| Placebo | DRUG | tablets packaged in bottles given orally once a day in the morning within approximately 10 minutes after breakfast |
| Aramchol meglumine | DRUG | Aramchol meglumine is a salt form of Aramchol free acid |
| Aramchol free acid | DRUG | Aramchol free acid is a fatty acid-bile acid conjugate |
| Aramchol free acid tablet 600mg, single dose | DRUG | Aramchol free acid tablet 600mg, single dose |
| Aramchol free acid tablet 300mg, bid | DRUG | Aramchol acid tablet 300mg, bid for 12 days |
| Midazolam | DRUG | Midazolam 2 mg |
| Atorvastatin | DRUG | atorvastatin 40 mg |
Inclusion Criteria: 1. Male or female age 18 to 75 years. 2. BMI between 25kg/m2 to 40kg/m2 or waist circumference between 88 cm to 200 cm for women, and between 102 cm to 200 cm for men. If there is deviation above the upper limit, please consult the MRI center, to ensure that the machine is suita...