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| ID | Type | Description | Link |
|---|---|---|---|
| 2021-006373-29 | EudraCT Number |
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The main aim is to check the effect of a single dose of soticlestat in adults with moderate or mild liver failure compared to healthy adults with normal liver function.
Participants will check into the study clinic for 8 days. During the stay, one oral dose of soticlestat will be given and the participant will be monitored. The clinic staff will follow up with the participant about a week after discharge from the clinic.
The drug being tested in this study is called soticlestat (TAK-935). The study will assess the safety and tolerability of single oral dose of soticlestat in participants with moderate or mild Hepatic Impairment (HI) compared to healthy participants matched by age (mean ±10 years), sex (±2 per sex), and body mass index (BMI, mean ±10 percent [%]) with normal hepatic function.
The study will enroll approximately 40 participants. Participants will be assigned to following study arms:
All participants will receive single oral dose of study drug. The data will be collected and stored in electronic case report form (eCRF).
This multi-center trial will be conducted in the United States and Hungary. The overall duration of the study is approximately 42 days. Participants will be followed up for 14 days after the last dose of study drug for a follow-up assessment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 1, Moderate HI: Soticlestat 300 mg | Experimental | Soticlestat 300 mg, tablets, orally, once on Day 1 to participant with moderate HI. |
|
| Arm 2, Mild HI: Soticlestat 300 mg | Experimental | Soticlestat 300 mg, tablets, orally, once on Day 1 to participant with mild HI. |
|
| Arm 3, Normal hepatic function: Soticlestat 300 mg | Experimental | Soticlestat 300 mg, tablets, orally, once on Day 1 to healthy participants. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Soticlestat | Drug | Soticlestat tablets. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Cmax: Maximum Observed Plasma Concentration for Soticlestat | Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose | |
| AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Time of Infinity for Soticlestat | Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose | |
| AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for Soticlestat | Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | An Adverse Event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE was defined as an AE that started or worsened at the time of or after dosing of study drug. |
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Inclusion Criteria A. For Participants with Hepatic Impairment
Has a BMI greater than or equal to (>=) 18.0 and less than or equal to (<=) 40.0 kilogram per square meter (kg/m^2), at screening. At least 50% of the participants will be required to be of BMI >=18.0 and <=35.0 kg/m^2, at screening.
Must have had chronic HI for at least 3 months before screening, and the HI must be stable, that is, no significant changes in hepatic function in the 30 days preceding screening (or since the last visit if within 6 months before screening) and treatment with stable doses of medication. Has a score on the Child-Pugh Class at screening as follows:
Should not have renal dysfunction as demonstrated by a relatively adequate renal function (creatinine clearance >=50 milliliter per minute [mL/min]), at screening.
B. For Healthy Participants
Has a BMI >=18.0 and <=40.0 kg/m^2, at screening. At least 50% of the participants will be required to be of BMI >=18.0 and <=35.0 kg/m^2, at screening. Healthy participants will be matched to hepatic impaired participants in this study by age (mean ±10 years), sex (±2 per sex), and BMI, mean ±10%.
Should not have renal dysfunction as demonstrated by a relatively adequate renal function (creatinine clearance >=60 mL/min), at screening.
C. For Participants with Hepatic Impairment and Healthy Participants
1. Continuous non-smoker or moderate smoker (<=10 cigarettes/day or the equivalent) before screening. Participant must agree to consume no more than 5 cigarettes or equivalent/day from the 7 days prior check-in and until discharge from the Clinical Research Unit (CRU).
Exclusion Criteria A. For Participants with Hepatic Impairment
B. For Healthy Participants
C. For Participants with Hepatic Impairment and Healthy Participants
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| Name | Affiliation | Role |
|---|---|---|
| Study Director | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Velocity | Edgewater | Florida | 32132 | United States | ||
| Clinical Pharmacology of Miami |
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| Label | URL |
|---|---|
| To obtain more information on the study, click here/on this link | View source |
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Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
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IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/ For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
Participants diagnosed with moderate/mild hepatic impairment (HI) compared to matched healthy participants with normal hepatic function received single dose of soticlestat. 1 with severe HI, 8 with moderate HI, 8 with mild HI and overall 19 participants with normal hepatic function (12 matched to moderate HI and 12 matched to mild HI participants) were enrolled. Five of same participants with normal hepatic function served as matched to moderate and mild HI.
Participants took part in the study at 4 investigative sites in the United States from 29 October 2021 to 07 June 2022.
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| ID | Title | Description |
|---|---|---|
| FG000 | Severe HI: Soticlestat 300 mg | Soticlestat 300 milligrams (mg), tablets, orally, once on Day 1 to participants with severe HI. |
| FG001 | Moderate HI: Soticlestat 300 mg | Soticlestat 300 mg, tablets, orally, once on Day 1 to participant with moderate HI. |
| FG002 | Mild HI: Soticlestat 300 mg | Soticlestat 300 mg, tablets, orally, once on Day 1 to participant with mild HI. |
| FG003 | Normal Hepatic Function: Soticlestat 300 mg | Soticlestat 300 mg, tablets, orally, once on Day 1 to healthy participants. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Safety analysis set included all participants who received the dose of soticlestat.
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| ID | Title | Description |
|---|---|---|
| BG000 | Severe HI: Soticlestat 300 mg | Soticlestat 300 mg, tablets, orally, once on Day 1 to participants with severe HI. |
| BG001 | Moderate HI: Soticlestat 300 mg | Soticlestat 300 mg, tablets, orally, once on Day 1 to participant with moderate HI. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Cmax: Maximum Observed Plasma Concentration for Soticlestat | Pharmacokinetic (PK) Analysis Set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (example, exposure to treatment, availability of measurements and absence of major protocol violations) and were included in the statistical analyses. Five of the same participants with normal hepatic function served as matched to moderate and mild HI arms. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram per milliliter (ng/mL) | Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose |
|
TEAEs were adverse events that started from Day 1 up to 16 days after the last dose of study drug (up to Day 17)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Severe HI: Soticlestat 300 mg | Soticlestat 300 mg, tablets, orally, once on Day 1 to participants with severe HI. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Alpha-1 acid glycoprotein increased | Investigations | MedDRA 24.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Takeda | +1-877-825-3327 | TrialDisclosures@takeda.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Apr 11, 2022 | May 30, 2023 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 12, 2022 | May 30, 2023 | SAP_001.pdf |
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| ID | Term |
|---|---|
| C000712808 | soticlestat |
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|
| From Day 1 up to 16 days after the last dose of study drug (up to Day 17) |
| Miami |
| Florida |
| 33014 |
| United States |
| Orlando Clinical Research Center | Orlando | Florida | 32809-3017 | United States |
| GCP | St. Petersburg | Florida | 33705 | United States |
| Texas Liver Institute | San Antonio | Texas | 78215 | United States |
| CRU Hungary Unit Pest Country Flor Ferenc Hospital | Kistarcsa | 2143 | Hungary |
| BG002 | Mild HI: Soticlestat 300 mg | Soticlestat 300 mg, tablets, orally, once on Day 1 to participant with mild HI. |
| BG003 | Normal Hepatic Function: Soticlestat 300 mg | Soticlestat 300 mg, tablets, orally, once on Day 1 to healthy participants. |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Body Mass Index (BMI) | Mean | Standard Deviation | kilogram per square meter (kg/m^2) |
|
| Height | Mean | Standard Deviation | centimeter (cm) |
|
| Weight | Mean | Standard Deviation | kilogram (kg) |
|
| Child-Pugh Score | The Child-Pugh classification score was used to determine the severity of hepatic impairment. A participant was rated a score of 1 to 3 for each of the 5 categories: encephalopathy, ascites, bilirubin, albumin and INR. The total score was the sum of the scores for each category with a minimum of 5 and a maximum of 15. A participant would have a mild hepatic impairment with a Child-Pugh score of 5 to 6, a moderate impairment with a score of 7 to 9 and a severe impairment with a score of 10 to 15. A participant with normal hepatic function would have a score of 0 assigned. | Here 'number analyzed' signifies that participant who were evaluable for this baseline measure. | Mean | Standard Deviation | score on scale |
|
Soticlestat 300 mg, tablets, orally, once on Day 1 to participant with moderate HI. |
| OG002 | Mild HI: Soticlestat 300 mg | Soticlestat 300 mg, tablets, orally, once on Day 1 to participant with mild HI. |
| OG003 | Normal Hepatic Function (Matched to Moderate HI): Soticlestat 300 mg | Soticlestat 300 mg, tablets, orally, once on Day 1 to healthy participants with normal hepatic function matched to moderate HI. |
| OG004 | Normal Hepatic Function (Matched to Mild HI): Soticlestat 300 mg | Soticlestat 300 mg, tablets, orally, once on Day 1 to healthy participants with normal hepatic function matched to mild HI. |
|
|
|
| Primary | AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Time of Infinity for Soticlestat | PK Analysis Set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (example, exposure to treatment, availability of measurements and absence of major protocol violations) and were included in the statistical analyses. Five of the same participants with normal hepatic function served as matched to moderate and mild HI arms. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram*hour per milliliter (ng•hr/mL) | Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose |
|
|
|
|
| Primary | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for Soticlestat | PK Analysis Set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (example, exposure to treatment, availability of measurements and absence of major protocol violations) and were included in the statistical analyses. Five of the same participants with normal hepatic function served as matched to moderate and mild HI arms. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose |
|
|
|
|
| Secondary | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | An Adverse Event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE was defined as an AE that started or worsened at the time of or after dosing of study drug. | Safety analysis set included all participants who received the dose of soticlestat. | Posted | Count of Participants | Participants | From Day 1 up to 16 days after the last dose of study drug (up to Day 17) |
|
|
|
| 0 |
| 1 |
| 0 |
| 1 |
| 1 |
| 1 |
| EG001 | Moderate HI: Soticlestat 300 mg | Soticlestat 300 mg, tablets, orally, once on Day 1 to participant with moderate HI. | 0 | 8 | 0 | 8 | 1 | 8 |
| EG002 | Mild HI: Soticlestat 300 mg | Soticlestat 300 mg, tablets, orally, once on Day 1 to participant with mild HI. | 0 | 8 | 0 | 8 | 1 | 8 |
| EG003 | Normal Hepatic Function: Soticlestat 300 mg | Soticlestat 300 mg, tablets, orally, once on Day 1 to healthy participants. | 0 | 19 | 0 | 19 | 2 | 19 |
| Constipation | Gastrointestinal disorders | MedDRA 24.1 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 24.1 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 24.1 | Systematic Assessment |
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| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 24.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 24.1 | Systematic Assessment |
|
Research Organization shall not publish any articles or papers nor make any presentations, nor assist any other person in publishing any articles or papers or in making any presentations relating or referring to the Study or any results, data or insights from or any data, information or materials obtained or generated in the performance of its obligations without the prior written consent of Takeda, which consent may be granted or withheld in Takeda's sole discretion.
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| GLSM Ratio |
| 130.25 |
| 2-Sided |
| 90 |
| 77.02 |
| 220.26 |
Geometric LSMs were calculated by exponentiating the LSMs from the mixed effects model. Geometric LSM Ratio (GMR) = 100*(Mild HI/Normal Hepatic Function (Matched to Mild HI) |
| Other |
| GLSM Ratio |
| 135.26 |
| 2-Sided |
| 90 |
| 91.22 |
| 200.57 |
Geometric LSMs were calculated by exponentiating the LSMs from the mixed effects model. Geometric LSM Ratio (GMR) = 100*(Mild HI/Normal Hepatic Function (Matched to Mild HI) |
| Other |