A Study of the Effectiveness of Armodafinil to Treat Cancer-Related Fatigue in Patients With Multiple Myeloma

This is a Phase III, multi-center, double-blind, randomized, placebo-controlled, crossover study to evaluate the efficacy of armodafinil at a dosage of 150 mg/day for the treatment of cancer-related fatigue (CRF) in adult patients with multiple myeloma. The study consists of a screening period, followed by a 56 day treatment phase, and a final assessment to occur 28 days after the end of the last treatment.

The screening period will occur within 14 days before baseline, where "baseline" refers to day 1 when assessments will be made before drug administration. During this period, a medical history will be obtained along with a complete physical examination including vital sign measurements and Eastern Cooperative Oncology Group (ECOG) performance status. Clinical laboratory tests including hematology, clinical chemistry (blood urea nitrogen [BUN], serum creatinine, total bilirubin, alkaline phosphatase, aspartate aminotransferase [AST] and alanine aminotransferase [ALT]), electrolytes (potassium, sodium, chloride and calcium), random glucose, total protein, albumin, and urinalysis will also be performed during the screening period as well as serum pregnancy tests for women of childbearing potential.

During the screening period, patients will also be assessed for the presence of cancer-related fatigue using the International Classification for Disease Tenth Edition (ICD-10) diagnostic criteria and the Brief Fatigue Inventory (BFI). Only those patients showing evidence of cancer-related fatigue will be enrolled in the study. The criteria for inclusion for any given patient consist of meeting the International Classification for Disease Tenth Edition (ICD-10) criteria for cancer-related fatigue and a score ≥ 4 on the BFI. ICD-10 CRF classification will be established using a standard interview guide.

Patients eligible for the study will be randomized to either receive armodafinil at an initial fixed dosage of 150 mg/day (Group A) or a placebo (Group B) during the first 28 days of the treatment phase. On day 29, patients randomized to receive placebo will then cross over to receive armodafinil at a dosage of 150 mg/day until day 56. Group A patients randomized to receive armodafinil will continue their current treatment with the drug until day 56. The duration of the treatment phase is 56 days.

Assessments for CRF will be conducted on day 1 (baseline) prior to drug treatment, and after drug administration on days 15, 28, 43, and 56. These assessments will be conducted as verbal interviews, paper-and-pencil surveys, paper-and-pencil tests, and electronic tests as appropriate per assessment.

During the treatment phase, each patient will also have clinical laboratory tests performed on days 1, 15, 28, 43 and 56 to monitor for potential toxicity. Additional procedures performed at these visits will include monitoring for adverse events, review of concomitant medications and other support therapies (e.g., growth factors and transfusion), ECOG performance status, vital signs measurements, and physical examinations.

Twenty-eight days after the last dose of study drug, patients are to complete a final assessment (herein referred to as the end-of-treatment visit). Procedures to be conducted at this visit include measurement of vital signs, a complete physical examination, assessment of adverse events, a review of concomitant medications, assessment of ECOG performance status, hematology and clinical chemistry laboratory tests including electrolytes, total protein and albumin. Patients who withdraw from the study before the completion of the 56 day cycle will still have all end-of-treatment assessments performed 28 days after their last dose of study drug.