Phase 1 Completed N=31 Randomized Other

Pharmacokinetics and Safety Study of Azacitidine in Cancer Patients With and Without Impaired Renal Function

MDS · AML · Solid Tumors · Multiple Myeloma

Source: ClinicalTrials.gov NCT00652626 ↗

Enrolled (actual)

Serious AEs

37.8%

Results posted

Oct 2013

Primary outcomePrimary: Area Under the Plasma Concentration-time Curve From Time 0 to 8 Hours Post-dose — 455.86; 897.43; 921.87; 1502.86 ng*hr/mL

Summary

The purpose of this study is to evaluate three things. The first being whether azacitidine is absorbed in the body at the same rate or proportion for different concentrations. The second is to determine the effect renal impairment has or does not have on the absorption of azacitidine. The third is to determine if azacitidine is safe and well tolerated in patients with renal function impairment.

Outcome Measures

Outcome	Result	p-value
PRIMARY Area Under the Plasma Concentration-time Curve From Time 0 to 8 Hours Post-dose	455.86; 897.43; 921.87; 1502.86	—
PRIMARY Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Time Point	454.80; 895.38; 920.76; 1505.16	—
PRIMARY Area Under the Plasma Concentration-time Curve From Time Zero to Infinity	460.47; 897.42; 945.50; 1533.37	—
PRIMARY Maximum Plasma Concentration of Azacitidine (Cmax)	293.38; 749.04; 745.50; 1261.96	—
PRIMARY Time to Maximum Plasma Concentration of Azacitidine (Tmax)	0.25; 0.25; 0.25; 0.27	—
PRIMARY Terminal Phase Half-life of Azacitidine (t½)	1.38; 0.63; 1.19; 1.03	—
PRIMARY Apparent Total Clearance of Azacitidine (CL/F)	104.58; 105.76; 151.55; 106.00	—
PRIMARY Apparent Volume of Distribution of Azacitidine (Vz/F)	208.69; 96.74; 259.44; 456.69	—
PRIMARY Area Under the Plasma Concentration-time Curve From Time 0 to 8 Hours Post-dose After Single and Multiple Doses of Azacitidine	921.87; 1558.32; 843.03; 1183.61	—
PRIMARY Area Under the Plasma Concentration-time Curve From Time 0 to the Last Quantifiable Time Point After Single and Multiple Doses of Azacitidine	920.76; 1558.72; 841.62; 1181.83	—
PRIMARY Area Under the Plasma Concentration-time Curve From Time 0 to Infinity After Single and Multiple Doses of Azacitidine	946.22; 1573.82; 857.64; 1210.92	—
PRIMARY Maximum Plasma Concentration of Azacitidine (Cmax) After Single and Multiple Doses of Azacitidine	745.50; 1056.66; 632.56; 668.11	—
PRIMARY Time to Maximum Plasma Concentration of Azacitidine (Tmax) After Single and Multiple Doses of Azacitidine	0.25; 0.50; 0.38; 0.64	0.1342
PRIMARY Terminal Phase Half-life of Azacitidine (t½) After Single and Multiple Doses of Azacitidine	1.19; 0.97; 1.03; 1.15	—
PRIMARY Apparent Total Clearance of Azacitidine (CL/F) After Single and Multiple Doses of Azacitidine	151.55; 85.76; 166.95; 111.55	—
PRIMARY Apparent Volume of Distribution of Azacitidine (Vz/F) After Single and Multiple Doses of Azacitidine	259.44; 120.47; 248.57; 184.54	—
PRIMARY Number of Participants With Adverse Events (AEs)	4; 3; 6; 5; 6; 14	—

Eligibility Criteria

Inclusion Criteria

Diagnosis of one of the following:
MDS according to the French-American-British (FAB) classification system: refractory anemia (RA), refractory anemia with ringed sideroblasts (RARS), refractory anemia with excess blasts (RAEB), refractory anemia with excess blasts in transformation (RAEB-T), or chronic myelomonocytic leukemia (CMML); or
Acute myelogenous leukemia (AML) in remission,
Malignant solid tumor,
Multiple myeloma (MM),
Non-Hodgkin lymphoma (NHL), or
Hodgkin lymphoma (HD)
Patients with a history of treated brain metastases should be clinically stable for greater than 4 weeks prior to signing the informed consent form and off glucocorticoid therapy for central nervous system (CNS) edema for at least 4 weeks
Be capable of giving informed consent
Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
Have a life expectancy ≥ 3 months
Have stable renal function for at least 2 months
Have average calculated creatinine clearance of:
>80 mL/min/1.73m^2 for Cohorts 1, 2, 3, and 4
<30 mL/min/1.73m^2 for Cohort 5 - Severe renal impairment,
50-80 mL/min/1.73m^2 for Cohort 6 - Mild renal impairment,
30 to <50 mL/min/1.73m^2 for Cohort 7 - Moderate renal impairment
Have organ and marrow function at the screening and pre-dose visits as defined below:
Hemoglobin ≥8 g/dL,
Absolute neutrophil count ≥0.75 x 10^3/µL,
Platelets ≥30 x 10^3/µL,
Total bilirubin ≤1.5 times the upper limit of normal (ULN),
Aspartate aminotransferase (AST) ≤2 times the ULN, and
Alanine transaminase (ALT) ≤2 times the ULN;
Have a 12-lead electrocardiogram (ECG) that is not clinically significant, as determined by the Investigator, at screening
Have serum bicarbonate:
20 mEq/L for patients with normal renal function (cohorts 1, 2, 3 and 4),
16 mEq/L for patients with impaired renal function (cohorts 5, 6 and 7)
Women of childbearing potential may participate, providing are not pregnant and agree to use at least 2 effective contraceptive methods throughout the study
Males with a female partner of childbearing potential must agree to use at least 2 effective contraceptive methods throughout the study and to avoid fathering a child for 6 months following the date of the last dose of study medication
Be a nonsmoker or must not have smoked for at least 30 days before the screening visit and agree to abstain from smoking during study participation

Exclusion Criteria

Women who are pregnant or nursing;
Had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to signing informed consent
Have been treated with an investigational agent within 4 weeks prior to signing the informed consent form
Have ongoing clinically significant adverse event(s) due to chemotherapy, radiotherapy or investigational agents administered more than 4 weeks prior to signing the informed consent as determined by the Investigator
Have known or suspected hypersensitivity to azacitidine or mannitol
Have an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia
Have low blood pressure (supine blood pressure <90/60 mmHg)
Have human immunodeficiency virus (HIV), or active hepatitis virus B or C
Have advanced malignant hepatic tumors
Have end stage renal disease requiring dialysis

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00652626). 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. Informational only — not medical advice.