Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as SHP626
Volixibat · 4 trials · 4 indications
The Adult ItchRO is an 11-point NRS measurement of itch severity ranging from 0=no itch to 10=worst possible itch.
TEAEs were defined as events that either had a start date on or after the first dose of investigational medicinal product (IMP) or has a start date before the date of the first dose of IMP, but increased in severity on or after the date of the first dose of IMP. An adverse event (AE) that occurred more than 9 days after the date of the last dose of double-blind IMP was not counted as a TEAE. Hematology parameters included evaluation of hemoglobin, hematocrit, red blood cells, platelets, white blood cell count; total and differential, neutrophils (absolute), eosinophils (absolute), monocytes (absolute), basophils (absolute) and lymphocytes (absolute).
TEAEs were defined as events that either had a start date on or after the first dose of IMP or has a start date before the date of the first dose of IMP, but increased in severity on or after the date of the first dose of IMP. An AE that occurred more than 9 days after the date of the last dose of double-blind IMP was not counted as a TEAE. Fat soluble vitamin included vitamin A (serum retinol), vitamin D (serum 25-hydroxycholecalciferol) and vitamin E (serum alfa-tocopherol).
TEAEs were defined as events that either had a start date on or after the first dose of IMP or has a start date before the date of the first dose of IMP, but increased in severity on or after the date of the first dose of IMP. An AE that occurred more than 9 days after the date of the last dose of double-blind IMP was not counted as a TEAE. Lipid panel parameters included evaluation of total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, very low-density lipoprotein (VLDL) cholesterol and low-density lipoprotein (LDL) cholesterol.
TEAEs were defined as events that either had a start date on or after the first dose of IMP or has a start date before the date of the first dose of IMP, but increased in severity on or after the date of the first dose of IMP. An AE that occurred more than 9 days after the date of the last dose of double-blind IMP was not counted as a TEAE. Thyroid hormone panel parameters included evaluation of thyroid hormones (TSH \[thyroid stimulating hormone\]; T3 \[triiodothyronine\] and T4 \[thyroxine\]).
TEAEs were defined as events that either had a start date on or after the first dose of IMP or has a start date before the date of the first dose of IMP, but increased in severity on or after the date of the first dose of IMP. An AE that occurred more than 9 days after the date of the last dose of double-blind IMP was not counted as a TEAE. Coagulation included international normalized ratio, activated partial thromboplastin time and prothrombin time.
TEAEs were defined as events that either had a start date on or after the first dose of IMP or has a start date before the date of the first dose of IMP, but increased in severity on or after the date of the first dose of IMP. An AE that occurred more than 9 days after the date of the last dose of double-blind IMP was not counted as a TEAE. Standard chemistry parameters included evaluation of sodium, potassium, glucose, blood urea nitrogen, creatinine, calcium, chloride, thyrotropin, thyroxine, tri-iodothyronine, phosphorus, protein, bicarbonate or carbon dioxide, albumin, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, alkaline phosphatase, total bilirubin, urate, beta-human chorionic gonadotropin and follicle-stimulating hormone levels. Participant with TEAE related to standard chemistry were reported with hepatic enzyme increase.
TEAEs were defined as events that either had a start date on or after the first dose of IMP or has a start date before the date of the first dose of IMP, but increased in severity on or after the date of the first dose of IMP. An AE that occurred more than 9 days after the date of the last dose of double-blind IMP was not counted as a TEAE. Urinalysis parameters included evaluation of pH, glucose, protein, nitrites, leukocyte esterase, occult blood, ketones, bilirubin and specific gravity levels.
TEAEs were defined as events that either had a start date on or after the first dose of IMP or has a start date before the date of the first dose of IMP, but increased in severity on or after the date of the first dose of IMP. An AE that occurred more than 9 days after the date of the last dose of double-blind IMP was not counted as a TEAE. Vital signs parameter included evaluation of orthostatic blood pressure, respiratory rate and body temperature.
TEAEs were defined as events that either had a start date on or after the first dose of IMP or has a start date before the date of the first dose of IMP, but increased in severity on or after the date of the first dose of IMP. An AE that occurred more than 9 days after the date of the last dose of double-blind IMP was not counted as a TEAE. Twelve lead electrocardiogram parameters \[(heart rate (HR), PR, RR, QRS and QT intervals and information on T-wave morphology (normal/abnormal) and U-wave morphology (absent/normal or abnormal)\] were assessed.
TEAEs were defined as events that either had a start date on or after the first dose of IMP or has a start date before the date of the first dose of IMP, but increased in severity on or after the date of the first dose of IMP. An AE that occurred more than 9 days after the date of the last dose of double-blind IMP was not counted as a TEAE.
TEAEs were defined as events that either had a start date on or after the first dose of IMP or has a start date before the date of the first dose of IMP, but increased in severity on or after the date of the first dose of IMP. An AE that occurred more than 9 days after the date of the last dose of double-blind IMP was not counted as a TEAE.
| Arm | Type | Description |
|---|---|---|
| Part 1 Arm 1: Volixibat 20mg | EXPERIMENTAL | Participants randomized to this arm will receive volixibat 20mg twice daily. |
| Part 1 Arm 2: Volixibat 80mg | EXPERIMENTAL | Participants randomized to this arm will receive volixibat 80mg twice daily. |
| Part 1 Arm 3: Placebo | PLACEBO_COMPARATOR | Participants in this arm will receive capsules matched to the study drug minus the active volixibat substance, twice daily. |
| Part 2 Arm 1: Volixibat Selected Dose 20mg | EXPERIMENTAL | Participants randomized to this arm will receive volixibat 20mg twice daily. |
| Part 2 Arm 2: Placebo | PLACEBO_COMPARATOR | Participants in this arm will receive capsules matched to the study drug minus the active volixibat substance, twice daily. |
| Experimental Drug | EXPERIMENTAL | single oral dose radiolabelled 50mg of SHP626 |
| SHP626 | EXPERIMENTAL | 9/12 subjects -1x daily dose of 20mg for 12 days 9/12 subjects-1x daily dose of 40mg for 12 days 9/12 subjects-1x daily dose of 80mg for 12 days 9/12 subjects-1x daily dose of 120mg for 12 days or dose lower than 80mg for 12 days 9/12 subjects-1x daily dose of 160mg for 12 days or dose lower than 80mg for 12 days 9/12 subjects-2x daily dose of SHP626 (dose TBD) for 12 days 9/12 subjects-2x daily dose of SHP626 (dose TBD; lower or higher than cohort 6) for 12 days 9/12 subjects-1x or 2x daily dose of SHP626 in an escalating titration (doses TBD). Initial 3 days of SHP626 followed by an increased dose of SHP626 for 3 days and finally a further increase in dose of SHP626 for 6 days 9/12 subjects will take a 1x or 2x daily dose of SHP626 in escalating titration (doses TBD; lower or higher dose than cohort 8). Initial 3 days of SHP626 followed by an increased dose of SHP626 for 3 days and finally a further increase in dose of SHP626 for 6 days |
| Placebo | PLACEBO_COMPARATOR | Three subjects per cohort will take a matched placebo |
| Name | Type | Description |
|---|---|---|
| Volixibat | DRUG | Oral capsules, administered twice daily. Volixibat is an Ileal Bile Acid Transporter (IBAT) inhibitor. |
| Placebo | DRUG | Capsules matched to study drug without the active pharmaceutical ingredient |
| SHP626 | DRUG | single oral dose 50mg SHP626 with approximately 5.95 μCi RAD |
| 5.95 μCi RAD | RADIATION | - |
Inclusion Criteria: * Provide signed informed consent at the screening visit as well as comply with all study visits and requirements through the end of the study * Male or female, age ≥18 years at the screening visit * Confirmed diagnosis of PBC in line with the AASLD guidelines * UDCA, anti-pruri...
Volixibat is an investigational small molecule being studied for itching caused by Primary Biliary Cholangitis (PBC) and Primary Sclerosing Cholangitis (PSC). It is currently in Phase 2 clinical development and is not yet approved by regulatory authorities.
Volixibat targets the SLC10A2 protein, also known as the apical sodium-dependent bile acid transporter. It acts as an inhibitor of this target, which is involved in the reabsorption of bile acids in the intestine.
Volixibat is being developed by Mirum Pharmaceuticals, Inc., a biopharmaceutical company. Mirum Pharmaceuticals is publicly traded under the ticker symbol MIRM on the NASDAQ stock exchange.
Volixibat is in Phase 2 clinical development. It is being evaluated in two active, placebo-controlled trials for itching associated with Primary Biliary Cholangitis and Primary Sclerosing Cholangitis. The drug is investigational and has not been approved.
Volixibat is being studied in two Phase 2 trials. NCT04663308 evaluates the drug in patients with itching caused by Primary Sclerosing Cholangitis, with an enrollment of 182. NCT05050136 evaluates it in patients with itching caused by Primary Biliary Cholangitis, with an enrollment of 333.
Volixibat is a distinct investigational drug with a unique mechanism of action, targeting SLC10A2. It is not known to be the same as any other approved or investigational therapy for Primary Biliary Cholangitis or Primary Sclerosing Cholangitis.