Desidustat in the Treatment of Chemotherapy Induced Anemia

A Phase 1, Open-Label, Single Dose, Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Desidustat for Treatment of Anemia in Patients Receiving Chemotherapy

This is a Phase 1, Open-label, Single Dose, Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Desidustat for treatment of anemia in patients receiving chemotherapy.

Study Overview

• Status: Completed
• Conditions: Anemia of Chronic Kidney Disease; Chemotherapy Effect
• Intervention / Treatment: Drug: Desidustat

Detailed Description

A total of up to approximately 24 patients will be enrolled to receive Desidustat in an open-label manner.

The study is divided into three cohorts as given below:

1. Cohort I: Single-dose 100 mg
2. Cohort II: Single-dose 150 mg
3. Cohort III: Single-dose 200 mg

Note:- After evaluation of PK data of 100 mg dose cohort, next cohort with higher dose will be decided. Maximum dose of Desidustat will not be exceeded than 200 mg.

First cohort will be given 100 mg single dose of Desidustat. On completion of safety and PK evaluation of first cohort,the next cohort with escalated single dose (150 mg) of Desidustat will be initiated. Similar way third cohort with 200 mg single dose will be initiated after safety evaluation of 150 mg cohort data.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• India
  • Mahar Ashtra
    • Nashik, Mahar Ashtra, India, 422002
      • HCG Manavata Cancer Centre,

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Diagnosis of non-myeloid malignancy.
2. Ability to comprehend and willingness to sign a written ICF for the study.
3. Male and Female patients at least 18 years old at the time of signing the ICF.
4. Anemia caused by cancer treatment (chemotherapy) defined as Hb ≤11.0 g/dL at screening.
5. Subjects with eGFR >60 mL/min/1.73 meter sequre at screening.
6. Weight should be ≥50 kg.
7. Willingness to participate after informed consent.
8. Females will not be pregnant or lactating, and females of childbearing potential and males will agree to use contraception.
9. Ability to swallow and retain oral medication.

Exclusion Criteria:

1. Known hypersensitivity to Desidustat and excipients in the investigational drug product.
2. History or presence of significant alcoholism, smoking or drug of abuse within 30 days at the time of screening.
3. History of RBC transfusion <4 weeks prior enrollment.
4. History or presence of any clinically significant electrocardiogram abnormalities during screening.
5. Cardiovascular risks, such as myocardial infarction, stroke, heart failure or thromboembolic event (e.g., deep vein thrombosis (DVT) or pulmonary embolism) within previous 6 months of screening
6. Major illness and/or major surgery in the last 3 months.
7. Planned elective surgery during the study
8. Receiving or has received any investigational drug within the 30 days before receiving Desidustat.
9. Any participants with poor peripheral venous access.
10. A positive test result for Human Immunodeficiency Virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibody at screening visit.

11. Female patients with following criteria will not be recruited:

    • History of pregnancy or lactation in the past 3 months
    • Fertile female volunteers not protected against pregnancy by adequate long-term antifertility measures
    • History of less than 1 year of menopause and not using adequate long-term anti-fertility measures
    • Using hormone replacement therapy
    • Unable to give assurance for protection against pregnancy for 3 months after the participation in this trial
    • Positive serum β-hCG level at the screening visit

12. Abnormal baseline laboratory investigations as follows:

    • WBC count ≤ 3 x 103/uL
    • Platelets count ≤ 100 x 103/uL
    • Bilirubin ≥ 1.5 mg/dL
    • ALT and/or AST ≥ 2.5 times of the ULN.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Desidustat tablet	Drug: Desidustat; A total of 24 participants will be enrolled. The study is divided into three cohorts as given below: Cohort I: Single-dose 100 mg; Cohort II: Single-dose 150 mg; Cohort III: Single-dose 200 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate Adverse event of Desidustat following a single oral dose of 100 or 150 or 200 mg in patients with chemotherapy induced anemia.	The Common Terminology Criteria for Adverse Event (CTCAE) (Version 4.03 or higher) system will be used for reporting and grading	Change from Baseline to Day 7 and Day 30

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of hemoglobin measurement from baseline	a single oral dose of 100 or 150 or 200 mg in patients with chemotherapy induced anemia.	Change from baseline to Day 7 and Day 30

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum plasma concentration (Cmax)	a single oral dose of 100 or 150 or 200 mg in patients with chemotherapy induced anemia. To compute pharmacokinetics, blood PK samples will be collected at pre-dose (<-0.5 h) and then 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 48.0 and 72.0 hour post the single dose administration. Patients will be discharged on Day 1 and provide Day 2 and Day 3 PK as an outpatient visit for PK draws.	Change from Baseline to 72 hours in blood
Time to reach maximum plasma concentration (Tmax)	a single oral dose of 100 or 150 or 200 mg in patients with chemotherapy induced anemia. To compute pharmacokinetics, blood PK samples will be collected at pre-dose (<-0.5 h) and then 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 48.0 and 72.0 hour post the single dose administration. Patients will be discharged on Day 1 and provide Day 2 and Day 3 PK as an outpatient visit for PK draws.	Change from Baseline to 72 hours in blood
Area under the curve from the time of dosing to the last measurable concentration (AUC0-t)	a single oral dose of 100 or 150 or 200 mg in patients with chemotherapy induced anemia. To compute pharmacokinetics, blood PK samples will be collected at pre-dose (<-0.5 h) and then 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 48.0 and 72.0 hour post the single dose administration. Patients will be discharged on Day 1 and provide Day 2 and Day 3 PK as an outpatient visit for PK draws.	Change from Baseline to 72 hours in blood
Terminal half life (t1/2)	a single oral dose of 100 or 150 or 200 mg in patients with chemotherapy induced anemia. To compute pharmacokinetics, blood PK samples will be collected at pre-dose (<-0.5 h) and then 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 48.0 and 72.0 hour post the single dose administration. Patients will be discharged on Day 1 and provide Day 2 and Day 3 PK as an outpatient visit for PK draws.	Change from Baseline to 72 hours in blood
Elimination rate constant (λz)	a single oral dose of 100 or 150 or 200 mg in patients with chemotherapy induced anemia. To compute pharmacokinetics, blood PK samples will be collected at pre-dose (<-0.5 h) and then 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 48.0 and 72.0 hour post the single dose administration. Patients will be discharged on Day 1 and provide Day 2 and Day 3 PK as an outpatient visit for PK draws.	Change from Baseline to 72 hours in blood
Clearance (CL)	a single oral dose of 100 or 150 or 200 mg in patients with chemotherapy induced anemia. To compute pharmacokinetics, blood PK samples will be collected at pre-dose (<-0.5 h) and then 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 48.0 and 72.0 hour post the single dose administration. Patients will be discharged on Day 1 and provide Day 2 and Day 3 PK as an outpatient visit for PK draws.	Change from Baseline to 72 hours in blood
Volume of distribution (Vd)	a single oral dose of 100 or 150 or 200 mg in patients with chemotherapy induced anemia. To compute pharmacokinetics, blood PK samples will be collected at pre-dose (<-0.5 h) and then 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 48.0 and 72.0 hour post the single dose administration. Patients will be discharged on Day 1 and provide Day 2 and Day 3 PK as an outpatient visit for PK draws.	Change from Baseline to 72 hours in blood
Amount recovered in Urine	Urine PK collection will occur relative to dosing of Desidustat at pre-dose (within 2 hours before dosing) and then at the proposed time points (0-6, 6-12 and 12-24 hr) for clearance. Desidustat and the drug metabolite in urine and additional assay may be required.	Change from baseline to 24 hours in urine
Percent recovered in urine	Urine PK collection will occur relative to dosing of Desidustat at pre-dose (within 2 hours before dosing) and then at the proposed time points (0-6, 6-12 and 12-24 hr) for clearance. Desidustat and the drug metabolite in urine and additional assay may be required.	Change from baseline to 24 hours in urine

Collaborators and Investigators

• Sponsor: Zydus Lifesciences Limited

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2020
• Primary Completion (Actual): March 27, 2022
• Study Completion (Actual): May 10, 2022

Study Registration Dates

• First Submitted: November 9, 2020
• First Submitted That Met QC Criteria: December 8, 2020
• First Posted (Actual): December 14, 2020

Study Record Updates

• Last Update Posted (Actual): May 18, 2022
• Last Update Submitted That Met QC Criteria: May 17, 2022
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Chemotherapy induced Anemia
• Additional Relevant MeSH Terms: Urologic Diseases; Hematologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic; Anemia
• Other Study ID Numbers: DESI.20.001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No