A Phase 1/2 interventional study of Tesevatinib in Polycystic Kidney, Autosomal Dominant, sponsored by Kadmon, a Sanofi Company. Completed at 11 sites in United States. Open to participants aged 18 Years to 62 Years. Per ClinicalTrials.gov, last updated 2022-11-08.
Sponsored by Kadmon, a Sanofi Company (part of Sanofi) · Phase 1/2, Interventional, and Treatment
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Among 85 studies in Polycystic Kidney, Autosomal Dominant with a site in United States — 14 open to participants now, 25 under way, 1 of them phase 3. Polycystic Kidney, Autosomal Dominant · United States.
Among the 85 studies in Polycystic Kidney, Autosomal Dominant with a site in United States, this one is the 26th largest by enrollment of the 63 interventional ones that give a count, is one of 2 that started in 2012, is one of 2 in phase 1/2, and was the 19th registered.
185 studies on the registry are indexed under Polycystic Kidney, Autosomal Dominant; 42 are open to participants now.
Browse Polycystic Kidney, Autosomal Dominant studies →14 of the 85 studies in Polycystic Kidney, Autosomal Dominant with a site in United States are open now. Recruiting first, the newest first:
Vertex Pharmaceuticals Incorporated · Sites in United States
Ages 19–55 · Men only · Healthy volunteers
Kenneth Hallows · Sites in United States
Ages 18–60
Mayo Clinic · Sites in United States
Ages 18–70
Richard Fatica · Sites in United States
Ages 18+
AstraZeneca · Sites in United States, China, United Kingdom
Ages 18–65
A study can be open while its sites in United States have not opened yet or have stopped. Only those recruiting at a site in United States →
Of the 30 Polycystic Kidney, Autosomal Dominant studies recruiting now, 8 (27%) set no upper age limit and 19 (63%) stop at 75 or younger; 7 take children under 18; 9 take healthy volunteers.
This study: 18 Years to 62 Years · all sexes · no healthy volunteers.
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85 studies; the count open now beside each. This study's row is marked.
A study in two phases is counted once above. Listed by phase, each with its combined phases: Phase 1 12 · Phase 2 25 · Phase 3 18 · Phase 4 2
First in 1998; this study’s year is marked. 2 started in 2012.
By drug class, each counting the studies that test any of its medicines:
This study's enrollment of 69 is above the median of 51 across 138 interventional studies indexed under Polycystic Kidney, Autosomal Dominant.
Median enrollment 48 across the 63 interventional studies, 90 across the 22 observational. Of the 59 that completed or were terminated, 34 (58%) have results posted.
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34 of 85 have an industry lead sponsor. The 10 most frequent:
This study is registered under Kadmon, a Sanofi Company, one of the names counted as Sanofi. Under that name alone:
Kadmon, a Sanofi Company is the lead sponsor of 14 studies on the registry; none are open to participants now.
Of its 9 completed or terminated interventional studies of FDA-regulated products, 6 (67%) have results posted.
Sanofi has 5 studies filed under Polycystic Kidney, Autosomal Dominant — fewer than ten, so there is no comparison to draw.
16 of the studies in Polycystic Kidney, Autosomal Dominant with a site in United States that are under way reach primary completion within a year, 0 of them phase 3. Phase 3 first, then by date:
| Study | Primary completion |
|---|---|
| NCT05193981Mayo ClinicA Study to Evaluate Homocysteine Metabolism and Endothelial Function in ADPKD | 2026-12 |
| NCT05288998Mayo ClinicIntrarenal Microvasculature in ADPKD | 2026-12 |
| NCT06786260Loma Linda UniversityDi-PKD: A Pilot Trial of Dietary Intervention in Patients With Autosomal Dominant Polycystic Kidney Disease | 2026-12 |
| NCT04344769Mayo ClinicCharacterization of the Nrf2 Response in Patients With Autosomal Dominant Polycystic Kidney Disease (ADPKD) | 2026-12 |
| NCT04630613Mayo ClinicNOX4 and Related Biomarkers in ADPKD | 2026-12 |
Add all 16 to your calendar (.ics) → With an account.
Among the 85 studies in Polycystic Kidney, Autosomal Dominant with a site in United States, from their registry updates:
This tab as a report to print or save as PDF → With an account.
The primary objective of this study Phase 1b was to determine the safety, plasma pharmacokinetics, and maximum tolerated dose (MTD) of tesevatinib when administered to participants with autosomal dominant polycystic kidney disease (ADPKD).
The primary objective of this study Phase 2a was to evaluate the annualized change in glomerular filtration rate (GFR) in participants with ADPKD when treated with tesevatinib.
Phase 1b:
Phase 2a:
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants received tesevatinib 50 milligrams (mg) tablet orally once daily (QD) for 28 days. After initial 28 days treatment, at the investigator's discretion, participants continued to receive tesevatinib for a total of 24 months (since treatment initiation) or until the development of unacceptable toxicity, noncompliance, or withdrawal of consent by the participant, or investigator decision (maximum duration: up to 36 months).
Drug: Tesevatinib
Participants received tesevatinib 100 mg tablet orally QD for 28 days. After initial 28 days treatment, at the investigator's discretion, participants continued to receive tesevatinib for a total of 24 months (since treatment initiation) or until the development of unacceptable toxicity, noncompliance, or withdrawal of consent by the participant, or investigator decision (maximum exposure duration: up to 36 months).
Drug: Tesevatinib
Participants received tesevatinib 150 mg tablet orally QD for 28 days. After initial 28 days treatment, at the investigator's discretion, participants continued to receive tesevatinib for a total of 24 months (since treatment initiation) or until the development of unacceptable toxicity, noncompliance, or withdrawal of consent by the participant, or investigator decision (maximum exposure duration: up to 36 months).
Drug: Tesevatinib
Participants received tesevatinib 150 mg tablet orally bi-weekly in alternative dosing schedules on Monday and Thursday for initial 25 days. After initial 25 days treatment, at the investigator's discretion, participants continued to receive tesevatinib for a total of 24 months (since treatment initiation) or until the development of unacceptable toxicity, noncompliance, or withdrawal of consent by the participant, or investigator decision (maximum exposure duration: up to 28 months).
Drug: Tesevatinib
Participants received tesevatinib 150 mg tablet orally tri-weekly in alternative dosing schedules on Monday, Wednesday and Friday for initial 26 days. After initial 26 days treatment, at the investigator's discretion, participants continued to receive tesevatinib for a total of 24 months (since treatment initiation) or until the development of unacceptable toxicity, noncompliance, or withdrawal of consent by the participant, or investigator decision (maximum exposure duration: up to 28 months).
Drug: Tesevatinib
Participants with autosomal dominant polycystic kidney disease (and Baseline estimated glomerular filtration rate (eGFR) greater than or equal to (\>=) 35 milliliters per minute per 1.73 square meter (mL/min/1.73 m\^2) and less than or equal to (\<=) 80 mL/min/1.73 m\^2, and height-adjusted total kidney volume (htTKV) \>=1000 mL were enrolled and received tesevatinib 50 mg tablet orally QD for initial 28 days. After initial 28 days treatment, at the investigator's discretion, participants continued to receive tesevatinib for a total of 24 months (since treatment initiation) or until the development of unacceptable toxicity, noncompliance, or withdrawal of consent by the participant, or investigator decision (maximum exposure duration: up to 28 months).
Drug: Tesevatinib
Pharmaceutical form: Tablets Route of administration: Oral
Also known as: XL647 and KD019
Phase 1b: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAE)
An adverse event (AE) was any untoward medical occurrence in a clinical study participant administered a medicinal product and which did not necessarily had to have a causal relationship with the treatment. An SAE was any untoward medical occurrence at any dose that: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs were AEs that developed or worsened or became serious from the first dose (Day 1) of the study drug until 30 days after the last dose of study drug.
Time frame: From Baseline (Day 1) until 30 days after the last dose of study drug (maximum duration: up to 37 months)
Phase 1b: Pharmacokinetics (PK): Plasma Concentrations of Tesevatinib 100 mg and 150 mg
Plasma concentrations of tesevatinib was analyzed using non-compartmental analysis.
Time frame: Pre-dose, 1, 2, 4, 8, and 24 hours post-dose on Day 1 and pre-dose, 1, 2, 4, and 24 hours post-dose on Day 14
Phase 1b: Pharmacokinetics: Plasma Concentrations of Tesevatinib 50 mg
Plasma concentrations of tesevatinib was analyzed using non-compartmental analysis.
Time frame: Pre-dose, 1, 2, 4, 8, and 24 hours post-dose on Day 1 and pre-dose, 1, 2, 4, and 24 hours post-dose on Day 14
Phase 1b: Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of Tesevatinib 100 mg and 150 mg
Cmax was defined as maximum observed plasma concentration.
Time frame: Pre-dose, 1, 2, 4, 8, and 24 hours post-dose on Day 1 and pre-dose, 1, 2, 4, and 24 hours post-dose on Day 14
Phase 1b: Pharmacokinetics: Maximum Observed Plasma Concentration of Tesevatinib 50 mg
Cmax was defined as maximum observed plasma concentration.
Time frame: Pre-dose, 1, 2, 4, 8, and 24 hours post-dose on Day 1 and pre-dose, 1, 2, 4, and 24 hours post-dose on Day 14
Phase 1b: Pharmacokinetics: Time of the Maximum Observed Plasma Concentration (Tmax) of Tesevatinib 100 mg and 150 mg
Tmax was defined as time to reach maximum observed plasma concentration.
Time frame: Pre-dose, 1, 2, 4, 8, and 24 hours post-dose on Day 1 and pre-dose, 1, 2, 4, and 24 hours post-dose on Day 14
Phase 1b: Pharmacokinetics: Time of the Maximum Observed Plasma Concentration of Tesevatinib 50 mg
Tmax was defined as time to reach maximum observed plasma concentration.
Time frame: Pre-dose, 1, 2, 4, 8, and 24 hours post-dose on Day 1 and pre-dose, 1, 2, 4, and 24 hours post-dose on Day 14
Phase 1b: Pharmacokinetics: Time of the Last Quantifiable Plasma Concentration (Tlast) of Tesevatinib 100 mg and 150 mg
Tlast was defined as time to reach last quantifiable plasma concentration.
Time frame: Pre-dose, 1, 2, 4, 8, and 24 hours post-dose on Day 1 and pre-dose, 1, 2, 4, and 24 hours post-dose on Day 14
Phase 1b: Pharmacokinetics: Time of the Last Quantifiable Plasma Concentration of Tesevatinib 50 mg
Tlast was defined as time to reach last quantifiable plasma concentration.
Time frame: Pre-dose, 1, 2, 4, 8, and 24 hours post-dose on Day 1 and pre-dose, 1, 2, 4, and 24 hours post-dose on Day 14
Phase 1b: Pharmacokinetics: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Quantifiable Concentration (AUC0-t) of Tesevatinib 100 mg and 150 mg
AUC0-last was defined as area under the concentration-time curve (AUC) from time 0 to the time of the last quantifiable concentration (tlast).
Time frame: Pre-dose, 1, 2, 4, 8, and 24 hours post-dose on day 1 and pre-dose, 1, 2, 4, and 24 hours post-dose on Day 14
Phase 1b: Pharmacokinetics: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Quantifiable Concentration of Tesevatinib 50 mg
AUC0-last was defined as area under the concentration-time curve (AUC) from time 0 to the time of the last quantifiable concentration (tlast).
Time frame: Pre-dose, 1, 2, 4, 8, and 24 hours post-dose on day 1 and pre-dose, 1, 2, 4, and 24 hours post-dose on Day 14
Phase 1b: Pharmacokinetics: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours Post-dose (AUC0-24) of Tesevatinib 100 mg and 150 mg
AUC0-24 was defined as area under the plasma concentration versus time curve of study drug from time 0 to 24 hours post-dose.
Time frame: Pre-dose, 1, 2, 4, 8, and 24 hours post-dose on Day 1 and pre-dose, 1, 2, 4, and 24 hours post-dose on Day 14
Phase 1b: Pharmacokinetics: Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours Post-dose of Tesevatinib 50 mg
AUC0-24 was defined as area under the plasma concentration versus time curve of study drug from time 0 to 24 hours post-dose.
Time frame: Pre-dose, 1, 2, 4, 8, and 24 hours post-dose on Day 1 and pre-dose, 1, 2, 4, and 24 hours post-dose on Day 14
Phase 1b: Pharmacokinetics: Trough Plasma Concentrations (Ctrough) of Tesevatinib 100 mg and 500 mg
Ctrough was the plasma concentration observed at the time immediately before (pre-dose) study drug administration.
Time frame: Pre-dose on Days 7, 14, 21, 28 and Months 2, 3, 4, 5 and 6
Phase 1b: Pharmacokinetics: Trough Plasma Concentrations of Tesevatinib 50 mg
Ctrough was the plasma concentration observed at the time immediately before study drug administration.
Time frame: Pre-dose on Days 7, 14, 21, 28 and Months 2, 3, 4, 5 and 6
Phase 1b: Maximum Tolerated Dose (MTD) of Tesevatinib
The MTD was determined based on dose-limiting toxicities (DLTs) occurring in the first 28 days of study treatment. Any toxicity that the Investigator and the Sponsor deemed to be dose-limiting, regardless of the grade, was considered as DLT.
Time frame: Cycle 1 (Up to 28 days)
Phase 2a: Annualized Percent Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)
eGFR: measures kidney function based on serum creatinine (Scr) and cystatin C (Scys). Annualized change in eGFR was calculated as: percent change from Baseline divided by total duration in days\*365.25. eGFR was estimated using 3 formulas and is reported separately for each formula: 1) 4-variable modification of diet in renal disease (MDRD-4) : Black/African-American males:175\*(Creatinine \[Cr\]\^-1.154)\*(Age\^-0.203)\*1.212, other males:175\*(Cr\^-1.154)\*(Age\^-0.203), females: male equation\*0.742.; 2) cystatin C-based chronic kidney disease (CKD) epidemiology (EPI) (CKD-EPI2012cys) equation: based on Scyc levels, for males if \<=0.8: 133\*(Scys/0.8)\^0.499\*0.996\^age, if \>0.8: 133\*(Scys/0.8)\^-1.238\*0.996\^age; for female: male equation\*0.932., 3) Scr- and Scys-based CKD-EPI (CKD EPI2012Scr-cys) equation: 135\*(Scr/0.9)\^XX\*(Scys/0.8)\^XXX\*0.995\^age\*(× 1.08, if black)- XX and XXX had variable values based on different values of Scr and Scys.
Time frame: Baseline (Day 1), Months 6, 12, 18, 24 and at end of study (i.e., anytime up to 37 months)
Phase 2a: Annualized Percent Change From Baseline in Height Adjusted Total Kidney Volume (htTKV) at Month 6, 12, 18, 24 and End of Study
htTKV was calculated using total kidney volume obtained from magnetic resonance imaging (MRI) divided by height in meters. The annualized percent change from Baseline was calculated as the percent change from Baseline divided by total duration in days\*365.25.
Time frame: Baseline (Day 1), Months 6, 12, 18, 24 and at end of study (i.e., anytime up to 37 months)
Phase 2a: Annualized Percent Change From Baseline in the Reciprocal of Serum Creatinine at End of Study
Reciprocal Creatinine was an indication for monitoring renal disease progression over time. The annualized percent change from Baseline was calculated as the percent change from Baseline divided by total duration in days\*365.25.
Time frame: Baseline (Day 1), at end of study (i.e., anytime up to 37 months)
Phase 2a: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (TESAE)
An AE was any untoward medical occurrence in a clinical study participant administered a medicinal product and which did not necessarily had to have a causal relationship with the treatment. An SAE was any untoward medical occurrence at any dose that: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs were AEs that developed or worsened or became serious from the first dose (Day 1) of the study drug until 30 days after the last dose of study drug.
Time frame: From Baseline (Day 1) until 30 days after the last dose of study drug (i.e., up to 29 months)
Phase 2a: Change From Baseline in Serum Creatinine Levels
Serum creatinine levels indicated the renal function (normal or abnormal) over time.
Time frame: Baseline, Day 1, 3, 7, 11, 12, 14, 21, 25, 26, 28, Month 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 16, 18, 20, 22, 24, and at end of study (i.e., anytime up to 37 months)
Phase 2a: Pharmacokinetics: Plasma Concentrations of Tesevatinib 150 mg
Plasma concentrations of tesevatinib was analyzed using non-compartmental analysis.
Time frame: Bi-weekly: pre-dose, 1, 2, 4, 8, and 24 hours post-dose on Day 1 and Day 25; Tri-weekly: pre-dose, 1, 2, 4, 8, and 24 hours post-dose on Day 1; pre-dose, 1, 2, 4, and 24 hours post-dose on Day 12
Phase 2a: Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of Tesevatinib 150 mg
Cmax was defined as maximum observed plasma concentration.
Time frame: Bi-weekly: pre-dose, 1, 2, 4, 8, and 24 hours post-dose on Day 1 and Day 25; Tri-weekly: pre-dose, 1, 2, 4, 8, and 24 hours post-dose on Day 1; pre-dose, 1, 2, 4, and 24 hours post-dose on Day 12
Phase 2a: Pharmacokinetics: Time of the Maximum Observed Plasma Concentration (Tmax) of Tesevatinib 150 mg
Tmax was defined as time to reach maximum observed plasma concentration.
Time frame: Bi-weekly: pre-dose, 1, 2, 4, 8, and 24 hours post-dose on Day 1 and Day 25; Tri-weekly: pre-dose, 1, 2, 4, 8, and 24 hours post-dose on Day 1; pre-dose, 1, 2, 4, and 24 hours post-dose on Day 12
Phase 2a: Pharmacokinetics: Time of the Last Quantifiable Plasma Concentration (Tlast) of Tesevatinib 150 mg
Tlast was defined as time to reach last quantifiable plasma concentration.
Time frame: Bi-weekly: pre-dose, 1, 2, 4, 8, and 24 hours post-dose on Day 1 and Day 25; Tri-weekly: pre-dose, 1, 2, 4, 8, and 24 hours post-dose on Day 1; pre-dose, 1, 2, 4, and 24 hours post-dose on Day 12
Phase 2a: Pharmacokinetics: Area Under the Plasma Concentration-time Curve From Time 0 to the Last Quantifiable Concentration (AUC0-t) of Tesevatinib 150 mg
AUC0-last was defined as area under the concentration-time curve (AUC) from time 0 to the time of the last quantifiable concentration (tlast).
Time frame: Bi-weekly: pre-dose, 1, 2, 4, 8, and 24 hours post-dose on Day 1 and Day 25; Tri-weekly: pre-dose, 1, 2, 4, 8, and 24 hours post-dose on Day 1; pre-dose, 1, 2, 4, and 24 hours post-dose on Day 12
Phase 2a: Pharmacokinetics: Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours Post-dose (AUC0-24) of Tesevatinib 150 mg
AUC0-24 was defined as area under the plasma concentration versus time curve of study drug from time 0 to 24 hours post-dose.
Time frame: Bi-weekly: pre-dose, 1, 2, 4, 8, and 24 hours post-dose on Day 1 and Day 25; Tri-weekly: pre-dose, 1, 2, 4, 8, and 24 hours post-dose on Day 1; pre-dose, 1, 2, 4, and 24 hours post-dose on Day 12
Phase 2a: Pharmacokinetics: Concentration Immediately Before Dosing (Ctrough) of Tesevatinib 150 mg
Ctrough was the plasma concentration observed at the time immediately before study drug administration.
Time frame: Bi-weekly: Pre-dose on Days 8, 11, 18 and 25; pre-dose on Months 2, 3, 4, 5 and 6; Tri-weekly: pre-dose on Days 3, 5, 8 and 12
The study was conducted at 11 active sites in the United States. A total of 126 participants were screened between 11 October 2012 and 07 March 2017, of which 69 participants were enrolled and treated.
| Milestone | Phase 1b: Cohort 1: Tesevatinib 50 mg Once Daily Dosing | Phase 1b: Cohort 2: Tesevatinib 100 mg Once Daily Dosing | Phase 1b: Cohort 3: Tesevatinib 150 mg Once Daily Dosing | Phase 2a: Cohort 4: Tesevatinib: Bi-weekly Dosing | Phase 2a: Cohort 5: Tesevatinib: Tri-weekly Dosing | Phase 2a: SILK Cohort: Tesevatinib 50 mg Once Daily Dosing |
|---|---|---|---|---|---|---|
| Started | 24 | 8 | 5 | 0 | 0 | 0 |
| Completed | 18 | 5 | 3 | 0 | 0 | 0 |
| Not completed | 6 | 3 | 2 | 0 | 0 | 0 |
| Withdrew: Withdrawal by subject | 2 | 1 | 1 | 0 | 0 | 0 |
| Withdrew: Investigator decision | 1 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Lost to follow-up | 1 | 1 | 0 | 0 | 0 | 0 |
| Withdrew: Adverse event or serious adverse event | 2 | 0 | 1 | 0 | 0 | 0 |
| Withdrew: Unspecified reason | 0 | 1 | 0 | 0 | 0 | 0 |
| Milestone | Phase 1b: Cohort 1: Tesevatinib 50 mg Once Daily Dosing | Phase 1b: Cohort 2: Tesevatinib 100 mg Once Daily Dosing | Phase 1b: Cohort 3: Tesevatinib 150 mg Once Daily Dosing | Phase 2a: Cohort 4: Tesevatinib: Bi-weekly Dosing | Phase 2a: Cohort 5: Tesevatinib: Tri-weekly Dosing | Phase 2a: SILK Cohort: Tesevatinib 50 mg Once Daily Dosing |
|---|---|---|---|---|---|---|
| Started | 0 | 0 | 0 | 10 | 14 | 8 |
| Completed | 0 | 0 | 0 | 8 | 13 | 8 |
| Not completed | 0 | 0 | 0 | 2 | 1 | 0 |
| Withdrew: Adverse event or serious adverse event | 0 | 0 | 0 | 1 | 1 | 0 |
| Withdrew: Unspecified reason | 0 | 0 | 0 | 1 | 0 | 0 |
An adverse event (AE) was any untoward medical occurrence in a clinical study participant administered a medicinal product and which did not necessarily had to have a causal relationship with the treatment. An SAE was any untoward medical occurrence at any dose that: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs were AEs that developed or worsened or became serious from the first dose (Day 1) of the study drug until 30 days after the last dose of study drug.
| Participants | Phase 1b: Cohort 1: Tesevatinib 50 mg Once Daily Dosing | Phase 1b: Cohort 2: Tesevatinib 100 mg Once Daily Dosing | Phase 1b: Cohort 3: Tesevatinib 150 mg Once Daily Dosing |
|---|---|---|---|
| TEAEs | 24 | 8 | 5 |
| SAE | 1 | 0 | 0 |
Plasma concentrations of tesevatinib was analyzed using non-compartmental analysis.
| nanograms per milliliter (ng/mL) | Phase 1b: Cohort 2: Tesevatinib 100 mg Once Daily Dosing | Phase 1b: Cohort 3: Tesevatinib 150 mg Once Daily Dosing |
|---|---|---|
| Day 1: Pre-dose | 0 ± 0 | 0 ± 0 |
| Day 1: 1 hour post-dose | 4.39 ± 2.78 | 8.41 ± 5.84 |
| Day 1: 2 hours post-dose | 10.1 ± 10.2 | 18.6 ± 12.0 |
| Day 1: 4 hours post-dose | 21.1 ± 14.8 | 33.1 ± 8.24 |
| Day 1: 8 hours post-dose | 25.4 ± 12.1 | 44.3 ± 7.50 |
| Day 1: 24 hours post-dose | 21.9 ± 9.69 | 35.5 ± 7.10 |
| Day 14: Pre-dose | 90.3 ± 29.1 | 164 ± 45.4 |
| Day 14: 1 hour post-dose | 94.0 ± 26.9 | 160 ± 37.2 |
| Day 14: 2 hours post-dose | 103 ± 29.4 | 180 ± 47.3 |
| Day 14: 4 hours post-dose | 111 ± 39.7 | 204 ± 66.8 |
| Day 14: 24 hours post-dose | 91.1 ± 28.9 | 150 ± 37.0 |
Plasma concentrations of tesevatinib was analyzed using non-compartmental analysis.
| ng/mL | Phase 1b: Cohort 1: Tesevatinib 50 mg Once Daily Dosing |
|---|---|
| Day 1: Pre-dose | 0 ± 0 |
| Day 1: 1 hour post-dose | 2.20 ± 2.06 |
| Day 1: 2 hours post-dose | 5.22 ± 3.58 |
| Day 1: 4 hours post-dose | 10.4 ± 4.77 |
| Day 1: 8 hours post-dose | 12.1 ± 5.74 |
| Day 1: 24 hours post-dose | 13.6 ± 4.18 |
| Day 14: Pre-dose | 54.4 ± 20.5 |
| Day 14: 1 hour post-dose | 56.8 ± 22.3 |
| Day 14: 2 hours post-dose | 58.5 ± 23.2 |
| Day 14: 4 hours post-dose | 63.2 ± 23.3 |
| Day 14: 24 hours post-dose | 55.8 ± 19.1 |
Cmax was defined as maximum observed plasma concentration.
| ng/mL | Phase 1b: Cohort 2: Tesevatinib 100 mg Once Daily Dosing | Phase 1b: Cohort 3: Tesevatinib 150 mg Once Daily Dosing |
|---|---|---|
| Day 1 | 27.5 ± 12.2 | 44.3 ± 7.50 |
| Day 14 | 116 ± 31.8 | 205 ± 65.4 |
Cmax was defined as maximum observed plasma concentration.
| ng/mL | Phase 1b: Cohort 1: Tesevatinib 50 mg Once Daily Dosing |
|---|---|
| Day 1 | 14.5 ± 5.34 |
| Day 14 | 65.9 ± 24.8 |
Tmax was defined as time to reach maximum observed plasma concentration.
| hours | Phase 1b: Cohort 2: Tesevatinib 100 mg Once Daily Dosing | Phase 1b: Cohort 3: Tesevatinib 150 mg Once Daily Dosing |
|---|---|---|
| Day 1 | 10.9 ± 8.09 | 7.99 ± 0.0434 |
| Day 14 | 6.25 ± 7.01 | 3.59 ± 0.891 |
Tmax was defined as time to reach maximum observed plasma concentration.
| hours | Phase 1b: Cohort 1: Tesevatinib 50 mg Once Daily Dosing |
|---|---|
| Day 1 | 16.4 ± 8.86 |
| Day 14 | 5.33 ± 6.34 |
Tlast was defined as time to reach last quantifiable plasma concentration.
| hours | Phase 1b: Cohort 2: Tesevatinib 100 mg Once Daily Dosing | Phase 1b: Cohort 3: Tesevatinib 150 mg |
|---|---|---|
| Day 1 | 23.9 ± 0.264 | 23.9 ± 0.132 |
| Day 14 | 23.5 ± 0.606 | 23.9 ± 0.154 |
Tlast was defined as time to reach last quantifiable plasma concentration.
| hours | Phase 1b: Cohort 1: Tesevatinib 50 mg Once Daily Dosing |
|---|---|
| Day 1 | 23.9 ± 0.177 |
| Day 14 | 23.9 ± 0.266 |
AUC0-last was defined as area under the concentration-time curve (AUC) from time 0 to the time of the last quantifiable concentration (tlast).
| hour*nanograms per milliliter (hr*ng/mL) | Phase 1b: Cohort 2: Tesevatinib 100 mg Once Daily Dosing | Phase 1b: Cohort 3: Tesevatinib 150 mg Once Daily Dosing |
|---|---|---|
| Day 1 | 508 ± 247 | 853 ± 130 |
| Day 14 | 2280 ± 741 | 4200 ± 1180 |
AUC0-last was defined as area under the concentration-time curve (AUC) from time 0 to the time of the last quantifiable concentration (tlast).
| hr*ng/mL | Phase 1b: Cohort 1: Tesevatinib 50 mg Once Daily Dosing |
|---|---|
| Day 1 | 272 ± 99.9 |
| Day 14 | 1410 ± 485 |
AUC0-24 was defined as area under the plasma concentration versus time curve of study drug from time 0 to 24 hours post-dose.
| hr*ng/mL | Phase 1b: Cohort 2: Tesevatinib 100 mg Once Daily Dosing | Phase 1b: Cohort 3: Tesevatinib 150 mg Once Daily Dosing |
|---|---|---|
| Day 1 | 507 ± 246 | 853 ± 129 |
| Day 14 | 2700 ± 750 | 4200 ± 1180 |
AUC0-24 was defined as area under the plasma concentration versus time curve of study drug from time 0 to 24 hours post-dose.
| hr*ng/mL | Phase 1b: Cohort 1: Tesevatinib 50 mg Once Daily Dosing |
|---|---|
| Day 1 | 272 ± 99.8 |
| Day 14 | 1430 ± 498 |
Ctrough was the plasma concentration observed at the time immediately before (pre-dose) study drug administration.
| ng/mL | Phase 1b: Cohort 2: Tesevatinib 100 mg Once Daily Dosing | Phase 1b: Cohort 3: Tesevatinib 150 mg Once Daily Dosing |
|---|---|---|
| Day 7: Pre-dose | 72.7 (52.0 to 108) | 143 (75.5 to 173) |
| Day 14: Pre-dose | 90.3 (52.8 to 131) | 164 (105 to 213) |
| Day 21: Pre-dose | 88.1 (5.74 to 122) | 155 (17.5 to 230) |
| Day 28: Pre-dose | 93.7 (22.9 to 135) | 180 (137 to 207) |
| Month 2: Pre-dose | 87.0 (17.1 to 142) | 107 (107 to 107) |
| Month 3: Pre-dose | 113 (80.3 to 152) | 130.25 (96.5 to 164) |
| Month 4: Pre-dose | 128 (83.4 to 173) | 121 (121 to 121) |
| Month 5: Pre-dose | 89.0 (66.4 to 116) | 227.5 (122 to 333) |
| Month 6: Pre-dose | 84.7 (63.2 to 112) | 119 (110 to 128) |
Ctrough was the plasma concentration observed at the time immediately before study drug administration.
| ng/mL | Phase 1b: Cohort 1: Tesevatinib 50 mg Once Daily Dosing |
|---|---|
| Day 7: Pre-dose | 45.4 ± 14.8 |
| Day 14: Pre-dose | 54.4 ± 20.5 |
| Day 21: Pre-dose | 59.9 ± 23.8 |
| Day 28: Pre-dose | 59.5 ± 26.7 |
| Month 2: Pre-dose | 54.9 ± 24.5 |
| Month 3: Pre-dose | 50.0 ± 21.8 |
| Month 4: Pre-dose | 45.5 ± 17.4 |
| Month 5: Pre-dose | 46.5 ± 16.3 |
| Month 6: Pre-dose | 44.8 ± 17.9 |
The MTD was determined based on dose-limiting toxicities (DLTs) occurring in the first 28 days of study treatment. Any toxicity that the Investigator and the Sponsor deemed to be dose-limiting, regardless of the grade, was considered as DLT.
| milligrams | Phase 1b: Cohort 1: Tesevatinib 50 mg Once Daily Dosing | Phase 1b: Cohort 2: Tesevatinib 100 mg Once Daily Dosing | Phase 1b: Cohort 3: Tesevatinib 150 mg Once Daily Dosing |
|---|---|---|---|
| Phase 1b: Maximum Tolerated Dose (MTD) of Tesevatinib | 100 | 100 | 100 |
eGFR: measures kidney function based on serum creatinine (Scr) and cystatin C (Scys). Annualized change in eGFR was calculated as: percent change from Baseline divided by total duration in days\*365.25. eGFR was estimated using 3 formulas and is reported separately for each formula: 1) 4-variable modification of diet in renal disease (MDRD-4) : Black/African-American males:175\*(Creatinine \[Cr\]\^-1.154)\*(Age\^-0.203)\*1.212, other males:175\*(Cr\^-1.154)\*(Age\^-0.203), females: male equation\*0.742.; 2) cystatin C-based chronic kidney disease (CKD) epidemiology (EPI) (CKD-EPI2012cys) equation: based on Scyc levels, for males if \<=0.8: 133\*(Scys/0.8)\^0.499\*0.996\^age, if \>0.8: 133\*(Scys/0.8)\^-1.238\*0.996\^age; for female: male equation\*0.932., 3) Scr- and Scys-based CKD-EPI (CKD EPI2012Scr-cys) equation: 135\*(Scr/0.9)\^XX\*(Scys/0.8)\^XXX\*0.995\^age\*(× 1.08, if black)- XX and XXX had variable values based on different values of Scr and Scys.
| percent change/participant-year | Phase 2a: Cohort 4: Tesevatinib: Bi-weekly Dosing | Phase 2a: Cohort 5: Tesevatinib: Tri-weekly Dosing | Phase 2a: SILK Cohort: Tesevatinib 50 mg Once Daily Dosing |
|---|---|---|---|
| Month 6: MDRD-4 | -0.125 ± 0.3236 | -0.150 ± 0.1515 | -0.195 ± 0.1851 |
| Month 6: CKD-EPI2012cys | 0.069 ± 0.2150 | 0.125 ± 0.1795 | 0.131 ± 0.2310 |
| Month 6: CKD-EPI2012Scr-cys | -0.031 ± 0.1522 | -0.009 ± 0.1277 | -0.043 ± 0.1341 |
| Month 12: MDRD-4 | -0.096 ± 0.1177 | -0.103 ± 0.1222 | -0.173 ± 0.0515 |
| Month 12: CKD-EPI2012cys | 0.040 ± 0.0644 | 0.031 ± 0.0696 | -0.037 ± 0.0966 |
| Month 12: CKD-EPI2012Scr-cys | -0.028 ± 0.0721 | -0.040 ± 0.0861 | -0.113 ± 0.0565 |
| Month 18: MDRD-4 | -0.087 ± 0.0680 | -0.060 ± 0.0402 | -0.121 ± 0.1002 |
| Month 18: CKD-EPI2012cys | 0.006 ± 0.0251 | 0.055 ± 0.0674 | 0.024 ± 0.1167 |
| Month 18: CKD-EPI2012Scr-cys | -0.040 ± 0.0379 | 0.000 ± 0.0463 | -0.056 ± 0.1049 |
| Month 24: MDRD-4 | -0.010 ± 0.0657 | -0.049 ± 0.0500 | -0.077 ± 0.0752 |
| Month 24: CKD-EPI2012cys | -0.000 ± 0.0245 | 0.029 ± 0.0388 | -0.017 ± 0.1081 |
| Month 24: CKD-EPI2012Scr-cys | -0.008 ± 0.0240 | -0.015 ± 0.0251 | -0.051 ± 0.0734 |
| End of study: MDRD-4 | -0.026 ± 0.2369 | -0.084 ± 0.1903 | -0.021 ± 0.0836 |
| End of study: CKD-EPI2012cys | 0.005 ± 0.0937 | 0.128 ± 0.2872 | -0.061 ± 0.0827 |
| End of study: CKD-EPI2012Scr-cys | -0.018 ± 0.1259 | 0.014 ± 0.0451 | -0.045 ± 0.0723 |
htTKV was calculated using total kidney volume obtained from magnetic resonance imaging (MRI) divided by height in meters. The annualized percent change from Baseline was calculated as the percent change from Baseline divided by total duration in days\*365.25.
| percent change/participant-year | Phase 2a: Cohort 4: Tesevatinib: Bi-weekly Dosing | Phase 2a: Cohort 5: Tesevatinib: Tri-weekly Dosing | Phase 2a: SILK Cohort: Tesevatinib 50 mg Once Daily Dosing |
|---|---|---|---|
| Month 6 | 0.0696 ± 0.1161 | 0.0544 ± 0.1292 | 0.1570 ± 0.0943 |
| Month 12 | 0.0503 ± 0.0758 | 0.0422 ± 0.0687 | 0.1145 ± 0.0722 |
| Month 18 | 0.0632 ± 0.0512 | 0.0353 ± 0.0483 | 0.0841 ± 0.0277 |
| Month 24 | 0.0702 ± 0.0517 | 0.0540 ± 0.0584 | 0.1080 ± 0.0536 |
| End of study | 0.0943 | 0.0517 ± 0.0327 | 0.0731 |
Reciprocal Creatinine was an indication for monitoring renal disease progression over time. The annualized percent change from Baseline was calculated as the percent change from Baseline divided by total duration in days\*365.25.
| percent change per participant-year | Phase 2a: Cohort 4: Tesevatinib: Bi-weekly Dosing | Phase 2a: Cohort 5: Tesevatinib: Tri-weekly Dosing | Phase 2a: SILK Cohort: Tesevatinib 50 mg Once Daily Dosing |
|---|---|---|---|
| Phase 2a: Annualized Percent Change From Baseline in the Reciprocal of Serum Creatinine at End of Study | -8.2923 ± 29.0965 | -6.9630 ± 20.2475 | 4.0189 ± 20.0561 |
An AE was any untoward medical occurrence in a clinical study participant administered a medicinal product and which did not necessarily had to have a causal relationship with the treatment. An SAE was any untoward medical occurrence at any dose that: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs were AEs that developed or worsened or became serious from the first dose (Day 1) of the study drug until 30 days after the last dose of study drug.
| Participants | Phase 2a: Cohort 4: Tesevatinib: Bi-weekly Dosing | Phase 2a: Cohort 5: Tesevatinib: Tri-weekly Dosing | Phase 2a: SILK Cohort: Tesevatinib 50 mg Once Daily Dosing |
|---|---|---|---|
| TEAEs | 10 | 14 | 8 |
| SAEs | 1 | 0 | 1 |
Serum creatinine levels indicated the renal function (normal or abnormal) over time.
| micromoles per liter | Phase 2a: Cohort 4: Tesevatinib: Bi-weekly Dosing | Phase 2a: Cohort 5: Tesevatinib: Tri-weekly Dosing | Phase 2a: SILK Cohort: Tesevatinib 50 mg Once Daily Dosing |
|---|---|---|---|
| Day 1 | — | — | 35.5 ± 34.6 |
| Day 3 | — | — | 9.8 ± 11.4 |
| Day 7 | — | — | 11.1 ± 15.6 |
| Day 11 | 4.5 ± 9.0 | — | — |
| Day 12 | — | 12.5 ± 8.5 | — |
| Day 14 | — | — | 8.3 ± 12.2 |
| Day 21 | — | — | 14.9 ± 17.5 |
| Day 25 | 5.3 ± 10.9 | — | — |
| Day 26 | — | 8.2 ± 6.4 | — |
| Day 28 | — | — | 14.9 ± 15.2 |
| Month 2 | 9.6 ± 14.1 | 5.8 ± 7.3 | 7.4 ± 20.5 |
| Month 3 | 8.4 ± 11.6 | 7.3 ± 8.6 | 10.8 ± 10.7 |
| Month 4 | 10.6 ± 14.0 | 4.5 ± 12.0 | 14.6 ± 12.4 |
| Month 5 | 4.4 ± 12.9 | 4.6 ± 6.9 | 7.1 ± 10.6 |
| Month 6 | 5.4 ± 11.0 | 5.5 ± 5.6 | 10.4 ± 9.9 |
| Month 7 | 9.6 ± 9.6 | 6.1 ± 6.0 | 24.9 ± 26.2 |
| Month 8 | 11.4 ± 11.1 | 5.4 ± 6.7 | 9.4 ± 8.3 |
| Month 9 | 10.6 ± 11.8 | 6.5 ± 7.7 | 12.0 ± 17.2 |
| Month 10 | 7.5 ± 13.7 | 2.6 ± 7.8 | 14.6 ± 9.0 |
| Month 11 | 12.1 ± 11.3 | 9.2 ± 9.5 | 13.3 ± 18.7 |
| Month 12 | 8.6 ± 10.4 | 8.0 ± 9.8 | 20.7 ± 9.7 |
| Month 13 | — | — | 0.0 |
| Month 14 | 6.1 ± 10.0 | 13.6 ± 9.8 | 13.3 ± 8.7 |
| Month 16 | 11.7 ± 11.5 | 6.7 ± 7.2 | 15.6 ± 13.1 |
| Month 18 | 11.4 ± 11.3 | 6.6 ± 4.2 | 21.6 ± 17.4 |
| Month 20 | 5.7 ± 11.4 | 4.6 ± 9.1 | 12.3 ± 26.9 |
| Month 22 | 6.7 ± 11.2 | 5.9 ± 10.3 | 12.3 ± 20.3 |
| Month 24 | 2.8 ± 10.6 | 7.0 ± 7.0 | 18.0 ± 20.6 |
| End of study | 5.5 ± 10.1 | 3.6 ± 8.3 | 6.3 ± 17.4 |
Plasma concentrations of tesevatinib was analyzed using non-compartmental analysis.
| ng/mL | Phase 2a: Cohort 4: Tesevatinib: Bi-weekly Dosing | Phase 2a: Cohort 5: Tesevatinib: Tri-weekly Dosing |
|---|---|---|
| Day 1: pre-dose | 0 ± 0 | 0 ± 0 |
| Day 1: 1 hour post-dose | 14.8 ± 18.9 | 13.0 ± 11.2 |
| Day 1: 2 hours post-dose | 21.7 ± 14.7 | 20.9 ± 12.7 |
| Day 1: 4 hours post-dose | 46.0 ± 16.2 | 41.1 ± 25.4 |
| Day 1: 8 hours post-dose | 55.0 ± 16.7 | 49.8 ± 19.9 |
| Day 1: 24 hours post-dose | 45.4 ± 8.81 | 42.4 ± 13.0 |
| Day 12: pre-dose | — | 53.7 ± 24.8 |
| Day 12: 1 hour post-dose | — | 58.5 ± 21.1 |
| Day 12: 2 hours post-dose | — | 70.1 ± 26.5 |
| Day 12: 4 hours post-dose | — | 100 ± 42.6 |
| Day 12: 24 hours post-dose | — | 90.5 ± 26.2 |
| Day 25: pre-dose | 29.6 ± 6.05 | — |
| Day 25: 1 hour post-dose | 31.9 ± 10.8 | — |
| Day 25: 2 hours post-dose | 50.5 ± 21.2 | — |
| Day 25: 4 hours post-dose | 76.2 ± 21.9 | — |
| Day 25: 8 hours post-dose | 83.9 ± 29.4 | — |
| Day 25: 24 hours post-dose | 69.4 ± 20.4 | — |
Cmax was defined as maximum observed plasma concentration.
| ng/mL | Phase 2a: Cohort 4: Tesevatinib: Bi-weekly Dosing | Phase 2a: Cohort 5: Tesevatinib: Tri-weekly Dosing |
|---|---|---|
| Day 1 | 56.1 ± 15.3 | 49.9 ± 20.3 |
| Day 12 | — | 102 ± 41.5 |
| Day 25 | 84.0 ± 29.2 | — |
Tmax was defined as time to reach maximum observed plasma concentration.
| hours | Phase 2a: Cohort 4: Tesevatinib: Bi-weekly Dosing | Phase 2a: Cohort 5: Tesevatinib: Tri-weekly Dosing |
|---|---|---|
| Day 1 | 14.5 ± 8.84 | 7.20 ± 1.76 |
| Day 12 | — | 12.0 ± 11.0 |
| Day 25 | 7.03 ± 2.02 | — |
Tlast was defined as time to reach last quantifiable plasma concentration.
| hours | Phase 2a: Cohort 4: Tesevatinib: Bi-weekly Dosing | Phase 2a: Cohort 5: Tesevatinib: Tri-weekly Dosing |
|---|---|---|
| Day 1 | 24.1 ± 0.163 | 20.8 ± 7.17 |
| Day 12 | — | 20.0 ± 8.95 |
| Day 25 | 24.2 ± 0.163 | — |
AUC0-last was defined as area under the concentration-time curve (AUC) from time 0 to the time of the last quantifiable concentration (tlast).
| hr*ng/mL | Phase 2a: Cohort 4: Tesevatinib: Bi-weekly Dosing | Phase 2a: Cohort 5: Tesevatinib: Tri-weekly Dosing |
|---|---|---|
| Day 1 | 1090 ± 274 | 866 ± 509 |
| Day 12 | — | 1860 ± 1160 |
| Day 25 | 1760 ± 559 | — |
AUC0-24 was defined as area under the plasma concentration versus time curve of study drug from time 0 to 24 hours post-dose.
| hr*ng/mL | Phase 2a: Cohort 4: Tesevatinib: Bi-weekly Dosing | Phase 2a: Cohort 5: Tesevatinib: Tri-weekly Dosing |
|---|---|---|
| Day 1 | 1090 ± 277 | 1020 ± 424 |
| Day 12 | — | 2280 ± 791 |
| Day 25 | 1740 ± 551 | — |
Ctrough was the plasma concentration observed at the time immediately before study drug administration.
| ng/mL | Phase 2a: Cohort 4: Tesevatinib: Bi-weekly Dosing | Phase 2a: Cohort 5: Tesevatinib: Tri-weekly Dosing |
|---|---|---|
| Day 3: Pre-dose | — | 37.2 (21.4 to 76.0) |
| Day 5: Pre-dose | — | 57.6 (34.2 to 116) |
| Day 8: Pre-dose | 28.0 (19.3 to 39.7) | 57.3 (30.7 to 132) |
| Day 11: Pre-dose | 38.8 (25.9 to 59.9) | — |
| Day 12: Pre-dose | — | 53.7 (29.9 to 95.2) |
| Day 18: Pre-dose | 33.6 (15.2 to 43.3) | — |
| Day 25: Pre-dose | 29.6 (20.6 to 33.9) | — |
| Month 2: Pre-dose | 34.1 (34.1 to 34.1) | — |
| Month 3: Pre-dose | 14.6 (14.6 to 14.6) | — |
| Month 4: Pre-dose | 47.55 (38.2 to 56.9) | — |
| Month 5: Pre-dose | 45.0 (25.4 to 64.6) | — |
| Month 6: Pre-dose | 21.6 (21.6 to 21.6) | — |
Collected over Phase 1b: From Baseline (Day 1) until 30 days after the last dose of study drug (i.e., up to 37 months) and Phase 2a: From Baseline (Day 1) until 30 days after the last dose of study drug (i.e., up to 29 months). Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Phase 1b: Cohort 1: Tesevatinib 50 mg Once Daily Dosing | 0/24 (0%) | 1/24 (4.2%) | 24/24 (100%) |
| Phase 1b: Cohort 2: Tesevatinib 100 mg Once Daily Dosing | 0/8 (0%) | 0/8 (0%) | 8/8 (100%) |
| Phase 1b: Cohort 3: Tesevatinib 150 mg Once Daily Dosing | 0/5 (0%) | 0/5 (0%) | 5/5 (100%) |
| Phase 2a: Cohort 4: Tesevatinib: Bi-weekly Dosing | 0/10 (0%) | 1/10 (10%) | 10/10 (100%) |
| Phase 2a: Cohort 5: Tesevatinib: Tri-weekly Dosing | 0/14 (0%) | 0/14 (0%) | 14/14 (100%) |
| Phase 2a: SILK Cohort: Tesevatinib 50 mg Once Daily Dosing | 0/8 (0%) | 1/8 (12.5%) | 8/8 (100%) |
| Event | Phase 1b: Cohort 1: Tesevatinib 50 mg Once Daily Dosing | Phase 1b: Cohort 2: Tesevatinib 100 mg Once Daily Dosing | Phase 1b: Cohort 3: Tesevatinib 150 mg Once Daily Dosing | Phase 2a: Cohort 4: Tesevatinib: Bi-weekly Dosing | Phase 2a: Cohort 5: Tesevatinib: Tri-weekly Dosing | Phase 2a: SILK Cohort: Tesevatinib 50 mg Once Daily Dosing |
|---|---|---|---|---|---|---|
| Herpes zosterInfections and infestations | 0/24 | 0/8 | 0/5 | 0/10 | 0/14 | 1/8 |
| Gastrooesophageal reflux diseaseGastrointestinal disorders | 0/24 | 0/8 | 0/5 | 1/10 | 0/14 | 0/8 |
| LacerationInjury, poisoning and procedural complications | 0/24 | 0/8 | 0/5 | 1/10 | 0/14 | 0/8 |
| DepressionPsychiatric disorders | 0/24 | 0/8 | 0/5 | 1/10 | 0/14 | 0/8 |
| Suicidal ideationPsychiatric disorders | 0/24 | 0/8 | 0/5 | 1/10 | 0/14 | 0/8 |
| AngioedemaSkin and subcutaneous tissue disorders | 1/24 | 0/8 | 0/5 | 0/10 | 0/14 | 0/8 |
| Event | Phase 1b: Cohort 1: Tesevatinib 50 mg Once Daily Dosing | Phase 1b: Cohort 2: Tesevatinib 100 mg Once Daily Dosing | Phase 1b: Cohort 3: Tesevatinib 150 mg Once Daily Dosing | Phase 2a: Cohort 4: Tesevatinib: Bi-weekly Dosing | Phase 2a: Cohort 5: Tesevatinib: Tri-weekly Dosing | Phase 2a: SILK Cohort: Tesevatinib 50 mg Once Daily Dosing |
|---|---|---|---|---|---|---|
| RashSkin and subcutaneous tissue disorders | 8/24 | 4/8 | 4/5 | 1/10 | 3/14 | 0/8 |
| DiarrhoeaGastrointestinal disorders | 10/24 | 4/8 | 2/5 | 5/10 | 6/14 | 2/8 |
| Muscle spasmsMusculoskeletal and connective tissue disorders | 5/24 | 2/8 | 0/5 | 0/10 | 5/14 | 4/8 |
| NauseaGastrointestinal disorders | 10/24 | 2/8 | 2/5 | 2/10 | 5/14 | 1/8 |
| Blood creatine phosphokinase increasedInvestigations | 7/24 | 3/8 | 0/5 | 4/10 | 5/14 | 1/8 |
| AcneSkin and subcutaneous tissue disorders | 4/24 | 0/8 | 2/5 | 2/10 | 1/14 | 1/8 |
| ProteinuriaRenal and urinary disorders | 4/24 | 0/8 | 2/5 | 0/10 | 0/14 | 0/8 |
| Blood creatinine increasedInvestigations | 4/24 | 3/8 | 1/5 | 1/10 | 2/14 | 2/8 |
| HypertensionVascular disorders | 4/24 | 0/8 | 0/5 | 1/10 | 2/14 | 3/8 |
| Amylase increasedInvestigations | 4/24 | 0/8 | 0/5 | 0/10 | 5/14 | 0/8 |
Analysis was performed on safety population which included all participants who receive at least 1 dose of tesevatinib.
| Age, Continuous(years) | Phase 1b: Cohort 1: Tesevatinib 50 mg Once Daily Dosing | Phase 1b: Cohort 2: Tesevatinib 100 mg Once Daily Dosing | Phase 1b: Cohort 3: Tesevatinib 150 mg Once Daily Dosing | Phase 2a: Cohort 4: Tesevatinib: Bi-weekly Dosing | Phase 2a: Cohort 5: Tesevatinib: Tri-weekly Dosing | Phase 2a: SILK Cohort: Tesevatinib 50 mg Once Daily Dosing | Total |
|---|---|---|---|---|---|---|---|
| Mean | 37.9 ± 9.1 | 36.6 ± 7.4 | 42.6 ± 4.4 | 34.9 ± 11.3 | 37.7 ± 11.1 | 52.1 ± 9.5 | 39.3 ± 10.5 |
| Sex: Female, Male(Participants) | Phase 1b: Cohort 1: Tesevatinib 50 mg Once Daily Dosing | Phase 1b: Cohort 2: Tesevatinib 100 mg Once Daily Dosing | Phase 1b: Cohort 3: Tesevatinib 150 mg Once Daily Dosing | Phase 2a: Cohort 4: Tesevatinib: Bi-weekly Dosing | Phase 2a: Cohort 5: Tesevatinib: Tri-weekly Dosing | Phase 2a: SILK Cohort: Tesevatinib 50 mg Once Daily Dosing | Total |
|---|---|---|---|---|---|---|---|
| Female | 15 | 3 | 3 | 6 | 10 | 3 | 40 |
| Male | 9 | 5 | 2 | 4 | 4 | 5 | 29 |
| Race/Ethnicity, Customized(Participants) | Phase 1b: Cohort 1: Tesevatinib 50 mg Once Daily Dosing | Phase 1b: Cohort 2: Tesevatinib 100 mg Once Daily Dosing | Phase 1b: Cohort 3: Tesevatinib 150 mg Once Daily Dosing | Phase 2a: Cohort 4: Tesevatinib: Bi-weekly Dosing | Phase 2a: Cohort 5: Tesevatinib: Tri-weekly Dosing | Phase 2a: SILK Cohort: Tesevatinib 50 mg Once Daily Dosing | Total |
|---|---|---|---|---|---|---|---|
| Asian | 3 | 0 | 0 | 0 | 0 | 0 | 3 |
| White | 20 | 8 | 5 | 8 | 14 | 7 | 62 |
| Black or African American | 1 | 0 | 0 | 2 | 0 | 0 | 3 |
| Other | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
Ran from Oct 2012 to primary completion in Feb 2019, 75 months.
Results were first posted in Nov 2022, 3 years 9 months after primary completion. A results delay was requested in Oct 2020.
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Studies of the drug tested here: XL647
Polycystic Kidney, Autosomal Dominant →