1 )]. 2 )]. 3 )]. 4) ]. The most common adverse reactions (≥10%) are fatigue, arthralgia, hypertension, nausea, edema, hypokalemia, hot flush, diarrhea, vomiting, upper respiratory infection, cough, and headache. 1 ) The most common laboratory abnormalities (>20%) are anemia, elevated alkaline phosphatase, hypertriglyceridemia, lymphopenia, hypercholesterolemia, hyperglycemia, and hypokalemia.
1 ) To report SUSPECTED ADVERSE REACTIONS, contact Dr. gov/medwatch. 1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
Two randomized placebo-controlled, multicenter clinical trials (COU-AA-301 and COU-AA302) enrolled patients who had metastatic CRPC in which abiraterone acetate was administered orally at a dose of 1,000 mg daily in combination with prednisone 5 mg twice daily in the active treatment arms.
Placebo plus prednisone 5 mg twice daily was given to patients on the control arm. Another randomized placebo-controlled, multicenter clinical trial (LATITUDE) enrolled patients who had metastatic high-risk CSPC in which abiraterone acetate was administered at a dose of 1,000 mg daily in combination with prednisone 5 mg once daily.
Placebos were administered to patients in the control arm. Additionally, two other randomized, placebo-controlled trials were conducted in patients with metastatic CRPC. The safety data pooled from 2,230 patients in the 5 randomized controlled trials constitute the basis for the data presented in the Warnings and Precautions, Grade 1 to 4 adverse reactions, and Grade 1 to 4 laboratory abnormalities.
In all trials, a gonadotropin-releasing hormone (GnRH) analog or prior orchiectomy was required in both arms. 1, 43) for placebo-treated patients. The most common adverse reactions (≥10%) that occurred more commonly (>2%) in the abiraterone acetate arm were fatigue, arthralgia, hypertension, nausea, edema, hypokalemia, hot flush, diarrhea, vomiting, upper respiratory infection, cough, and headache.
The most common laboratory abnormalities (>20%) that occurred more commonly (≥2%) in the abiraterone acetate arm were anemia, elevated alkaline phosphatase, hypertriglyceridemia, lymphopenia, hypercholesterolemia, hyperglycemia, and hypokalemia.
Grades 3 to 4 adverse events were reported for 53% of patients in the abiraterone acetate arm and 46% of patients in the placebo arm. Treatment discontinuation was reported in 14% of patients in the abiraterone acetate arm and 13% of patients in the placebo arm.
The common adverse events (≥1%) resulting in discontinuation of abiraterone acetate and prednisone were hepatotoxicity and cardiac disorders. 6% of patients in the placebo arm. 3%). Other reported causes of death in >5 patients included pneumonia, cardio-respiratory arrest, death (no additional information), and general physical health deterioration.
COU-AA-301:
Metastatic CRPC Following Chemotherapy COU-AA-301 enrolled 1,195 patients with metastatic CRPC who had received prior docetaxel chemotherapy. 5 x ULN in the absence of liver metastases. Patients with liver metastases were excluded if AST and/or ALT >5 x ULN.
Table 1 shows adverse reactions on the abiraterone acetate arm in COU-AA-301 that occurred with a ≥ 2% absolute increase in frequency compared to placebo or were events of special interest. The median duration of treatment with abiraterone acetate with prednisone was 8 months.
0. 2 Includes terms Arthritis, Arthralgia, Joint swelling, and Joint stiffness. 3 Includes terms Muscle spasms, Musculoskeletal pain, Myalgia, Musculoskeletal discomfort, and Musculoskeletal stiffness . 4 Includes terms Edema, Edema peripheral, Pitting edema, and Generalized edema.
5 Includes all fractures with the exception of pathological fracture . 6 Includes terms Arrhythmia, Tachycardia, Atrial fibrillation, Supraventricular tachycardia, Atrial tachycardia, Ventricular tachycardia, Atrial flutter, Bradycardia, Atrioventricular block complete, Conduction disorder, and Bradyarrhythmia.
7 Includes terms Angina pectoris, Chest pain, and Angina unstable. 3% vs. 1% respectively). 8 Includes terms Cardiac failure, Cardiac failure congestive, Left ventricular dysfunction, Cardiogenic shock, Cardiomegaly, Cardiomyopathy, and Ejection fraction decreased.
Table 2 shows laboratory abnormalities of interest from COU-AA-301. 8 0 COU-AA-302 : Metastatic CRPC Prior to Chemotherapy COU-AA-302 enrolled 1,088 patients with metastatic CRPC who had not received prior cytotoxic chemotherapy. 5 x ULN and patients were excluded if they had liver metastases.
Table 3 shows adverse reactions on the abiraterone acetate arm in COU-AA-302 that occurred in ≥5% of patients with a ≥2% absolute increase in frequency compared to placebo. 8 months. 0. 2 Includes terms Edema peripheral, Pitting edema, and Generalized edema.
3 Includes terms Arthritis, Arthralgia, Joint swelling, and Joint stiffness. Table 4 shows laboratory abnormalities that occurred in greater than 15% of patients, and more frequently (>5%) in the abiraterone acetate arm compared to placebo in COU-AA-302.
Table 4:
Laboratory Abnormalities in >15% of Patients in the Abiraterone Acetate Arm of COU-AA-302. 7 1 Based on non-fasting blood draws.
LATITUDE:
Patients with Metastatic High-risk CSPC LATITUDE enrolled 1,199 patients with newly-diagnosed metastatic, high-risk CSPC who had not received prior cytotoxic chemotherapy. 5 x ULN or if they had liver metastases. All the patients received GnRH analogs or had prior bilateral orchiectomy during the trial.
The median duration of treatment with abiraterone acetate and prednisone was 24 months. Table 5 shows adverse reactions on the abiraterone acetate arm that occurred in ≥5% of patients with a ≥2% absolute increase in frequency compared to those on the placebos arm.
2 0 1 All patients were receiving an GnRH agonist or had undergone orchiectomy. 0 3 Reported as an adverse event or reaction 4 Including cough, productive cough, upper airway cough syndrome Table 6 shows laboratory abnormalities that occurred in >15% of patients, and more frequently (>5%) in the abiraterone acetate arm compared to placebos.
9%). 3% of patients taking abiraterone acetate and led to 5 treatment discontinuations and 4 deaths. 2% of patients taking placebo. There were no treatment discontinuations and two deaths due to cardiac failure in the placebo group. In the same combined data, the majority of arrhythmias were grade 1 or 2.
There was one death associated with arrhythmia and three patients with sudden death in the abiraterone acetate arms and five deaths in the placebo arms. 1%) deaths in the placebo arms. Myocardial ischemia or myocardial infarction led to death in 3 patients in the placebo arms and 3 deaths in the abiraterone acetate arms.
2 Postmarketing Experien ce The following additional adverse reactions have been identified during post approval use of abiraterone acetate with prednisone. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Respiratory, Thoracic and Mediastinal Disorders : non-infectious pneumonitis. Musculoskeletal and Connective Tissue Disorders : myopathy, including rhabdomyolysis. Hepatobiliary Disorders: fulminant hepatitis, including acute hepatic failure and death.
Cardiac Disorders:
QT prolongation and Torsades de Pointes (observed in patients who developed hypokalemia or had underlying cardiovascular conditions). Immune System Disorders – Hypersensitivity: anaphylactic reactions (severe allergic reactions that include, but are not limited to difficulty swallowing or breathing, swollen face, lips, tongue or throat, or an itchy rash (urticaria)).