Anemia of Chronic Kidney Disease, Chemotherapy Effect
Conditions
Keywords
Chemotherapy induced Anemia
Brief 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.
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.
Interventions
DRUGDesidustat
A total of 24 participants will be enrolled. 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
Sponsors
Zydus Lifesciences Limited
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate Adverse event of Desidustat following 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 | The Common Terminology Criteria for Adverse Event (CTCAE) (Version 4.03 or higher) system will be used for reporting and grading |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change of hemoglobin measurement from baseline | Change from baseline to Day 7 and Day 30 | a single oral dose of 100 or 150 or 200 mg in patients with chemotherapy induced anemia. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Area under the curve from the time of dosing to the last measurable concentration (AUC0-t) | Change from Baseline to 72 hours in blood | 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. |
| Terminal half life (t1/2) | Change from Baseline to 72 hours in blood | 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. |
| Clearance (CL) | Change from Baseline to 72 hours in blood | 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. |
| Maximum plasma concentration (Cmax) | Change from Baseline to 72 hours in blood | 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. |
| Volume of distribution (Vd) | Change from Baseline to 72 hours in blood | 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. |
| Amount recovered in Urine | Change from baseline to 24 hours 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. |
| Percent recovered in urine | Change from baseline to 24 hours 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. |
| Elimination rate constant (λz) | Change from Baseline to 72 hours in blood | 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. |
| Time to reach maximum plasma concentration (Tmax) | Change from Baseline to 72 hours in blood | 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. |
Countries
India
Outcome results
None listed