Polycystic Kidney, Autosomal DominantPhase 1/2NCT01559363

A Safety, Pharmacokinetic & Dose-Escalation Study of KD019 in Subjects With Autosomal Dominant Polycystic Kidney Disease

A Phase 1/2 study testing Tesevatinib in people with Polycystic Kidney, Autosomal Dominant, run by Kadmon, a Sanofi Company at 11 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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). Read more about this study

Who is it for?: Ages 18 to 62 years
Conditions the study is for: Polycystic Kidney, Autosomal Dominant
What is being tested?: Tesevatinib
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 69 participants
Where: 11 sitesUnited States
Study dates: 11 Oct 2012to 8 Feb 2019
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 62 years
All sexes
No healthy volunteers
Adult

Who may be able to join

The participant had a confirmed diagnosis of ADPKD.
The participant had a GFR >=35 mL/min/1.73m^2.
Cysts must be at least 1 centimeter in size.
Adequate bone marrow, kidney, and liver function.
Must agree to use two forms of birth control for those of child bearing potential.
Normal amylase and lipase levels.
The participant had a htTKV >= 1000 mL (htTKV was calculated using total kidney volume obtained from magnetic resonance imaging divided by height in meters).

Who cannot join

The participant has had a previous partial or total nephrectomy.
The participant had tuberous sclerosis, Hippel-Lindau disease, or acquired cystic disease.
The participant had congenital absence of one kidney and/or need for dialysis.
Presence of renal or hepatic calculi (stones) causing symptoms.
The participant had received any investigational therapy within 30 days prior to study entry.
Active treatment (within 4 weeks of study entry) for urinary tract infection.

Show all 13Show fewer

Participant was known to be immunocompromised.
Participant was pregnant or nursing.
History of pericardial effusion or presence of pericardial effusion on screening echocardiogram
Uncontrolled hypertension.
History of pancreatitis or had known risk factors for pancreatitis.
Participant had received EGFR inhibitor at any time.
The participant was aphakic due to previous cataract surgery or congenital anomaly.

Trial locations and contacts

11 sites in 1 country.

City, postcode or hospital

11 sites in 1 country

United States11 sites

Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
University of Virginia - Nephrology Clinical Research Center
Charlottesville, Virginia, 22908
Cleveland Clinic
Cleveland, Ohio, 44195
University of Colorado Denver
Denver, Colorado, 80045
University of Kansas Medical Center
Kansas City, Kansas, 66160
UCLA Medical Center
Los Angeles, California, 90025
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
New York University School of Medicine
New York, New York, 10016
Mayo Clinic
Rochester, Minnesota, 55905
Clinical Advancement Center, PLLC
San Antonio, Texas, 78215
Washington University School of Medicine
St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: A Phase 1b/2a, Safety, Pharmacokinetic and Dose-Escalation Study of KD019 (Tesevatinib) in Subjects 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.

Read the detailed description

Phase 1b:

Primary objective was to determine the safety of tesevatinib.
Dosing was for 28 days daily. After the 28-day treatment period, participants would, at the discretion of the investigator, continue to receive study treatment for 24 months from their first dose or until the development of unacceptable toxicity, noncompliance, or withdrawal of consent by the participant, or investigator decision. Participants might continue beyond 24 months at the discretion of the investigator after consultation with the medical monitor.
All participants received active tesevatinib study drug.
Tesevatinib is an oral once daily tablet. Tablets were 50 milligrams (mg), 100 mg and 150 mg in strength. Participants were enrolled into three sequential dosing cohort levels (50 mg, 100 mg and 150 mg.). Participants in Phase 1b had their dose increased or decreased to the maximum tolerated dose (MTD).
Study participants had magnetic resonance imaging (MRI) of the abdomen (kidneys) at Screening and 6 months thereafter to explore effects of KD019.
Echocardiogram was performed at Screening, Day 28, months 3 and 6 and every 6 months thereafter.

Phase 2a:

Primary objective was to compare the annualized change in GFR in participants with ADPKD when treated with tesevatinib.
Two alternate dosing schedules were explored to determine if they were more tolerable than daily dosing when used chronically in participants with ADPKD.
Participants received study treatment for 24 months from their first dose or until the development of unacceptable toxicity, noncompliance, or withdrawal of consent by the participant, or investigator decision. Participants continued beyond 24 months at the discretion of the investigator after consultation with the sponsor.
All participants received active tesevatinib study drug.
Tablets were 50 mg, 100 mg, and 150 mg in strength.
Study participants had MRI of the abdomen (kidneys) at Screening and Month 6 visit and every 6 months after to explore effects of tesevatinib.
Echocardiogram was performed at Screening, Day 28, and Months 3 and 6 and 6 months thereafter.

Conditions: Polycystic Kidney, Autosomal Dominant
Being tested: Tesevatinib
Medical subject headings: Polycystic Kidney, Autosomal Dominant

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

TesevatinibDrug
Also called XL647 and KD019
Pharmaceutical form: Tablets Route of administration: Oral

Study groups in NCT01559363
Study group	Role	What they receive
Phase 1b: Cohort 1: Tesevatinib 50 mg Once Daily Dosing	Experimental	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). Receives: Drug: Tesevatinib
Phase 1b: Cohort 2: Tesevatinib 100 mg Once Daily Dosing	Experimental	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). Receives: Drug: Tesevatinib
Phase 1b: Cohort 3: Tesevatinib 150 mg Once Daily Dosing	Experimental	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). Receives: Drug: Tesevatinib
Phase 2a: Cohort 4: Tesevatinib: Bi-weekly Dosing	Experimental	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). Receives: Drug: Tesevatinib
Phase 2a: Cohort 5: Tesevatinib: Tri-weekly Dosing	Experimental	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). Receives: Drug: Tesevatinib
Phase 2a: Safety in Larger Kidneys (SILK) Cohort: Tesevatinib 50 mg Once Daily Dosing	Experimental	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). Receives: Drug: Tesevatinib

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline (Day 1), Months 6, 12, 18, 24 and at end of study (i.e., anytime up to 37 months)

Secondary outcomes (11)

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

11 Oct 20128 Feb 2019

First posted21 Mar 2012 (estimated)
Study start11 Oct 2012
Primary completion8 Feb 2019
Study completion8 Feb 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Polycystic Kidney, Autosomal DominantStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Enrolment: 69 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01559363
Sponsor's protocol ID: KD019-101
Other IDs: U1111-1279-2764, MAD17715
Status last verified: Oct 2022
First submitted: 9 Mar 2012
Last updated: 8 Nov 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: 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

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 8 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1b/2a, Safety, Pharmacokinetic and Dose-Escalation Study of KD019 (Tesevatinib) in Subjects With Autosomal Dominant Polycystic Kidney Disease (ADPKD)
ClinicalTrials.gov ID: NCT01559363
Acronym / sponsor ID: KD019-101
Conditions: Polycystic Kidney, Autosomal Dominant
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 69 participants (actual)
Lead sponsor: Kadmon, a Sanofi CompanyIndustry (pharma, biotech, devices)
Study start: 11 Oct 2012 (actual)
Primary completion: 8 Feb 2019 (actual)
Study completion: 8 Feb 2019 (actual)
First posted: 21 Mar 2012 (estimated)
Results: Posted 8 Nov 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Detailed description

Phase 1b:

Primary objective was to determine the safety of tesevatinib.
Dosing was for 28 days daily. After the 28-day treatment period, participants would, at the discretion of the investigator, continue to receive study treatment for 24 months from their first dose or until the development of unacceptable toxicity, noncompliance, or withdrawal of consent by the participant, or investigator decision. Participants might continue beyond 24 months at the discretion of the investigator after consultation with the medical monitor.
All participants received active tesevatinib study drug.
Tesevatinib is an oral once daily tablet. Tablets were 50 milligrams (mg), 100 mg and 150 mg in strength. Participants were enrolled into three sequential dosing cohort levels (50 mg, 100 mg and 150 mg.). Participants in Phase 1b had their dose increased or decreased to the maximum tolerated dose (MTD).
Study participants had magnetic resonance imaging (MRI) of the abdomen (kidneys) at Screening and 6 months thereafter to explore effects of KD019.
Echocardiogram was performed at Screening, Day 28, months 3 and 6 and every 6 months thereafter.

Phase 2a:

Primary objective was to compare the annualized change in GFR in participants with ADPKD when treated with tesevatinib.
Two alternate dosing schedules were explored to determine if they were more tolerable than daily dosing when used chronically in participants with ADPKD.
Participants received study treatment for 24 months from their first dose or until the development of unacceptable toxicity, noncompliance, or withdrawal of consent by the participant, or investigator decision. Participants continued beyond 24 months at the discretion of the investigator after consultation with the sponsor.
All participants received active tesevatinib study drug.
Tablets were 50 mg, 100 mg, and 150 mg in strength.
Study participants had MRI of the abdomen (kidneys) at Screening and Month 6 visit and every 6 months after to explore effects of tesevatinib.
Echocardiogram was performed at Screening, Day 28, and Months 3 and 6 and 6 months thereafter.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 6

Arm	Type	Receives
Phase 1b: Cohort 1: Tesevatinib 50 mg Once Daily Dosing	Experimental	Drug: TesevatinibParticipants 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).
Phase 1b: Cohort 2: Tesevatinib 100 mg Once Daily Dosing	Experimental	Drug: TesevatinibParticipants 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).
Phase 1b: Cohort 3: Tesevatinib 150 mg Once Daily Dosing	Experimental	Drug: TesevatinibParticipants 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).
Phase 2a: Cohort 4: Tesevatinib: Bi-weekly Dosing	Experimental	Drug: TesevatinibParticipants 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).
Phase 2a: Cohort 5: Tesevatinib: Tri-weekly Dosing	Experimental	Drug: TesevatinibParticipants 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).
Phase 2a: Safety in Larger Kidneys (SILK) Cohort: Tesevatinib 50 mg Once Daily Dosing	Experimental	Drug: TesevatinibParticipants 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).

Who may qualify

Ages: 18 to 62 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (7 listed)

The participant had a confirmed diagnosis of ADPKD.
The participant had a GFR >=35 mL/min/1.73m^2.
Cysts must be at least 1 centimeter in size.
Adequate bone marrow, kidney, and liver function.
Must agree to use two forms of birth control for those of child bearing potential.

Key exclusion criteria (13 listed)

The participant has had a previous partial or total nephrectomy.
The participant had tuberous sclerosis, Hippel-Lindau disease, or acquired cystic disease.
The participant had congenital absence of one kidney and/or need for dialysis.
Presence of renal or hepatic calculi (stones) causing symptoms.
The participant had received any investigational therapy within 30 days prior to study entry.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
TesevatinibAlso: XL647 and KD019Pharmaceutical form: Tablets Route of administration: Oral	Drug	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: Safety in Larger Kidneys (SILK) Cohort: Tesevatinib 50 mg Once Daily Dosing

Primary outcome

Phase 1b: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAE)
Time frame: From Baseline (Day 1) until 30 days after the last dose of study drug (maximum duration: up to 37 months)
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.
Phase 1b: Pharmacokinetics (PK): Plasma Concentrations of Tesevatinib 100 mg and 150 mg
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
Plasma concentrations of tesevatinib was analyzed using non-compartmental analysis.
Phase 1b: Pharmacokinetics: Plasma Concentrations of Tesevatinib 50 mg
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
Plasma concentrations of tesevatinib was analyzed using non-compartmental analysis.
Phase 1b: Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of Tesevatinib 100 mg and 150 mg
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
Cmax was defined as maximum observed plasma concentration.
Phase 1b: Pharmacokinetics: Maximum Observed Plasma Concentration of Tesevatinib 50 mg
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
Cmax was defined as maximum observed plasma concentration.
Phase 1b: Pharmacokinetics: Time of the Maximum Observed Plasma Concentration (Tmax) of Tesevatinib 100 mg and 150 mg
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
Tmax was defined as time to reach maximum observed plasma concentration.
Phase 1b: Pharmacokinetics: Time of the Maximum Observed Plasma Concentration of Tesevatinib 50 mg
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
Tmax was defined as time to reach maximum observed plasma concentration.
Phase 1b: Pharmacokinetics: Time of the Last Quantifiable Plasma Concentration (Tlast) of Tesevatinib 100 mg and 150 mg
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
Tlast was defined as time to reach last quantifiable plasma concentration.
Phase 1b: Pharmacokinetics: Time of the Last Quantifiable Plasma Concentration of Tesevatinib 50 mg
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
Tlast was defined as time to reach last quantifiable plasma concentration.
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
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
AUC0-last was defined as area under the concentration-time curve (AUC) from time 0 to the time of the last quantifiable concentration (tlast).
Phase 1b: Pharmacokinetics: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Quantifiable Concentration of Tesevatinib 50 mg
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
AUC0-last was defined as area under the concentration-time curve (AUC) from time 0 to the time of the last quantifiable concentration (tlast).
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
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
AUC0-24 was defined as area under the plasma concentration versus time curve of study drug from time 0 to 24 hours post-dose.
Phase 1b: Pharmacokinetics: Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours Post-dose of Tesevatinib 50 mg
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
AUC0-24 was defined as area under the plasma concentration versus time curve of study drug from time 0 to 24 hours post-dose.
Phase 1b: Pharmacokinetics: Trough Plasma Concentrations (Ctrough) of Tesevatinib 100 mg and 500 mg
Time frame: Pre-dose on Days 7, 14, 21, 28 and Months 2, 3, 4, 5 and 6
Ctrough was the plasma concentration observed at the time immediately before (pre-dose) study drug administration.
Phase 1b: Pharmacokinetics: Trough Plasma Concentrations of Tesevatinib 50 mg
Time frame: Pre-dose on Days 7, 14, 21, 28 and Months 2, 3, 4, 5 and 6
Ctrough was the plasma concentration observed at the time immediately before study drug administration.
Phase 1b: Maximum Tolerated Dose (MTD) of Tesevatinib
Time frame: Cycle 1 (Up to 28 days)
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.
Phase 2a: Annualized Percent Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)
Time frame: Baseline (Day 1), Months 6, 12, 18, 24 and at end of study (i.e., anytime up to 37 months)
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.

11 secondary outcomes

Phase 2a: Annualized Percent Change From Baseline in Height Adjusted Total Kidney Volume (htTKV) at Month 6, 12, 18, 24 and End of Study
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
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)
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
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
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
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
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
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
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
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
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

Results and safety

Results posted to the registry on 8 Nov 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Phase 1b: Cohort 1: Tesevatinib 50 mg Once Daily Dosing	24	18
Phase 1b: Cohort 2: Tesevatinib 100 mg Once Daily Dosing	8	5
Phase 1b: Cohort 3: Tesevatinib 150 mg Once Daily Dosing	5	3
Phase 2a: Cohort 4: Tesevatinib: Bi-weekly Dosing	0	0
Phase 2a: Cohort 5: Tesevatinib: Tri-weekly Dosing	0	0
Phase 2a: SILK Cohort: Tesevatinib 50 mg Once Daily Dosing	0	0

Primary outcome: Phase 1b: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAE)

Time frame: From Baseline (Day 1) until 30 days after the last dose of study drug (maximum duration: up to 37 months). Count of participants. Unit: Participants

Measure	Phase 1b: Cohort 1: Tesevatinib 50 mg Once Daily Dosing n = 24	Phase 1b: Cohort 2: Tesevatinib 100 mg Once Daily Dosing n = 8	Phase 1b: Cohort 3: Tesevatinib 150 mg Once Daily Dosing n = 5
TEAEs	24	8	5
SAE	1	0	0

Population analysed: Analysis was performed on safety population.

Primary outcome: Phase 1b: Pharmacokinetics (PK): Plasma Concentrations of Tesevatinib 100 mg and 150 mg

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. Mean (Standard Deviation). Unit: nanograms per milliliter (ng/mL)

Measure	Phase 1b: Cohort 2: Tesevatinib 100 mg Once Daily Dosing n = 8	Phase 1b: Cohort 3: Tesevatinib 150 mg Once Daily Dosing n = 5
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)

Population analysed: Analysis was performed on PK Population which consisted of all participants who received at least one dose of tesevatinib 100 mg (in Phase 1b: Cohort 2) and 150 mg (in Phase 1b: Cohort 3) and had quantifiable PK data available. Here, 'number analyzed' = participants with available data for each specified category.

Primary outcome: Phase 1b: Pharmacokinetics: Plasma Concentrations of Tesevatinib 50 mg

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. Mean (Standard Deviation). Unit: ng/mL

Measure	Phase 1b: Cohort 1: Tesevatinib 50 mg Once Daily Dosing n = 23
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)

Population analysed: Analysis was performed on PK Population which consisted of all participants who received at least one dose of tesevatinib 50 mg in Phase 1b and had quantifiable PK data available. Here, overall number of participants analyzed = participants evaluable for this outcome measure (OM) and 'number analyzed' = participants with available data for each specified category.

Primary outcome: Phase 1b: Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of Tesevatinib 100 mg and 150 mg

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. Mean (Standard Deviation). Unit: ng/mL

Measure	Phase 1b: Cohort 2: Tesevatinib 100 mg Once Daily Dosing n = 8	Phase 1b: Cohort 3: Tesevatinib 150 mg Once Daily Dosing n = 5
Day 1	27.5 (12.2)	44.3 (7.50)
Day 14	116 (31.8)	205 (65.4)

Population analysed: Analysis was performed on PK Population.

11 secondary outcomes are reported in the full results.

Adverse events

Time frame: 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). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Phase 1b: Cohort 1: Tesevatinib 50 mg Once Daily Dosing	1 of 24 (4.2%)	24 of 24 (100%)	0 of 24
Phase 1b: Cohort 2: Tesevatinib 100 mg Once Daily Dosing	0 of 8 (0%)	8 of 8 (100%)	0 of 8
Phase 1b: Cohort 3: Tesevatinib 150 mg Once Daily Dosing	0 of 5 (0%)	5 of 5 (100%)	0 of 5
Phase 2a: Cohort 4: Tesevatinib: Bi-weekly Dosing	1 of 10 (10%)	10 of 10 (100%)	0 of 10
Phase 2a: Cohort 5: Tesevatinib: Tri-weekly Dosing	0 of 14 (0%)	14 of 14 (100%)	0 of 14
Phase 2a: SILK Cohort: Tesevatinib 50 mg Once Daily Dosing	1 of 8 (12.5%)	8 of 8 (100%)	0 of 8

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Nov 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: 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

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

11 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Tesevatinib in people with Polycystic Kidney, Autosomal Dominant, run by Kadmon, a Sanofi Company at 11 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Nov 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase 1b: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAE) (time frame: From Baseline (Day 1) until 30 days after the last dose of study drug (maximum duration: up to 37 months)). The study lists 17 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01559363.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Nov 2022.