Desidustat in the Treatment of Chemotherapy Induced Anemia

Chemotherapy Effect Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04667533
• Other study ID #: DESI.20.001
• Status: Completed
• Phase: Phase 1
• Start date: November 11, 2020
• Est. completion date: May 10, 2022

Study information

• Verified date: November 2020
• Source: Cadila Healthcare Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: May 10, 2022
• Est. primary completion date: March 27, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

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 ß-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.

Related Conditions & MeSH terms

• Anemia
• Anemia of Chronic Kidney Disease
• Chemotherapy Effect
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

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

Locations

Country	Name	City	State
India	HCG Manavata Cancer Centre,	Nashik	Mahar Ashtra

Sponsors (1)

Lead Sponsor	Collaborator
Cadila Healthcare Limited

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Other	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
Other	Elimination rate constant (?z)	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
Other	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
Other	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
Other	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
Other	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
Primary	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	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