Phase 2
N=37
A Safety, Pharmacokinetic & Dose-Escalation Study of KD019 in Subjects With Autosomal Dominant Polycystic Kidney Disease
Polycystic Kidney, Autosomal Dominant
Bottom Line
View on ClinicalTrials.gov: NCT01559363 ↗Enrolled (actual)
37
Serious AEs
4.4%
Results posted
Nov 2022
Primary outcome: Primary: Phase 1b: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAE) — 24; 8; 5; 1 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Tesevatinib (Drug)
- Age
- Adult · 18+ yrs
- Sex
- All
- Sponsor
- Kadmon, a Sanofi Company
- Primary completion
- Feb 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Phase 1b: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAE) |
24; 8; 5; 1; 0; 0 | — |
| PRIMARY Phase 1b: Pharmacokinetics (PK): Plasma Concentrations of Tesevatinib 100 mg and 150 mg |
0; 0; 4.39; 8.41; 10.1; 18.6 | — |
| PRIMARY Phase 1b: Pharmacokinetics: Plasma Concentrations of Tesevatinib 50 mg |
0; 2.20; 5.22; 10.4; 12.1; 13.6 | — |
| PRIMARY Phase 1b: Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of Tesevatinib 100 mg and 150 mg |
27.5; 44.3; 116; 205 | — |
| PRIMARY Phase 1b: Pharmacokinetics: Maximum Observed Plasma Concentration of Tesevatinib 50 mg |
14.5; 65.9 | — |
| PRIMARY Phase 1b: Pharmacokinetics: Time of the Maximum Observed Plasma Concentration (Tmax) of Tesevatinib 100 mg and 150 mg |
10.9; 7.99; 6.25; 3.59 | — |
| PRIMARY Phase 1b: Pharmacokinetics: Time of the Maximum Observed Plasma Concentration of Tesevatinib 50 mg |
16.4; 5.33 | — |
| PRIMARY Phase 1b: Pharmacokinetics: Time of the Last Quantifiable Plasma Concentration (Tlast) of Tesevatinib 100 mg and 150 mg |
23.9; 23.9; 23.5; 23.9 | — |
| PRIMARY Phase 1b: Pharmacokinetics: Time of the Last Quantifiable Plasma Concentration of Tesevatinib 50 mg |
23.9; 23.9 | — |
| PRIMARY 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 |
508; 853; 2280; 4200 | — |
| PRIMARY Phase 1b: Pharmacokinetics: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Quantifiable Concentration of Tesevatinib 50 mg |
272; 1410 | — |
| PRIMARY 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 |
507; 853; 2700; 4200 | — |
| PRIMARY Phase 1b: Pharmacokinetics: Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours Post-dose of Tesevatinib 50 mg |
272; 1430 | — |
| PRIMARY Phase 1b: Pharmacokinetics: Trough Plasma Concentrations (Ctrough) of Tesevatinib 100 mg and 500 mg |
72.7; 143; 90.3; 164; 88.1; 155 | — |
| PRIMARY Phase 1b: Pharmacokinetics: Trough Plasma Concentrations of Tesevatinib 50 mg |
45.4; 54.4; 59.9; 59.5; 54.9; 50.0 | — |
| PRIMARY Phase 1b: Maximum Tolerated Dose (MTD) of Tesevatinib |
100; 100; 100 | — |
| PRIMARY Phase 2a: Annualized Percent Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) |
-0.125; -0.150; -0.195; 0.069; 0.125; 0.131 | — |
| SECONDARY Phase 2a: Annualized Percent Change From Baseline in Height Adjusted Total Kidney Volume (htTKV) at Month 6, 12, 18, 24 and End of Study |
0.0696; 0.0544; 0.1570; 0.0503; 0.0422; 0.1145 | — |
| SECONDARY Phase 2a: Annualized Percent Change From Baseline in the Reciprocal of Serum Creatinine at End of Study |
-8.2923; -6.9630; 4.0189 | — |
| SECONDARY Phase 2a: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (TESAE) |
10; 14; 8; 1; 0; 1 | — |
| SECONDARY Phase 2a: Change From Baseline in Serum Creatinine Levels |
35.5; 9.8; 11.1; 4.5; 12.5; 8.3 | — |
| SECONDARY Phase 2a: Pharmacokinetics: Plasma Concentrations of Tesevatinib 150 mg |
0; 0; 14.8; 13.0; 21.7; 20.9 | — |
| SECONDARY Phase 2a: Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of Tesevatinib 150 mg |
56.1; 49.9; 102; 84.0 | — |
| SECONDARY Phase 2a: Pharmacokinetics: Time of the Maximum Observed Plasma Concentration (Tmax) of Tesevatinib 150 mg |
14.5; 7.20; 12.0; 7.03 | — |
| SECONDARY Phase 2a: Pharmacokinetics: Time of the Last Quantifiable Plasma Concentration (Tlast) of Tesevatinib 150 mg |
24.1; 20.8; 20.0; 24.2 | — |
| SECONDARY Phase 2a: Pharmacokinetics: Area Under the Plasma Concentration-time Curve From Time 0 to the Last Quantifiable Concentration (AUC0-t) of Tesevatinib 150 mg |
1090; 866; 1860; 1760 | — |
| SECONDARY Phase 2a: Pharmacokinetics: Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours Post-dose (AUC0-24) of Tesevatinib 150 mg |
1090; 1020; 2280; 1740 | — |
| SECONDARY Phase 2a: Pharmacokinetics: Concentration Immediately Before Dosing (Ctrough) of Tesevatinib 150 mg |
37.2; 57.6; 28.0; 57.3; 38.8; 53.7 | — |
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).
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.
Eligibility Criteria
Inclusion Criteria
- 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).
Exclusion Criteria
- 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.
- 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.
Data sourced from ClinicalTrials.gov (NCT01559363). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.