Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.
Clinical Trials Experience
CKD Stages 3 and 4
The safety of Zemplar Capsules has been evaluated in three 24-week (approximately six-month), double-blind, placebo-controlled, multicenter clinical studies involving 220 CKD Stages 3 and 4 patients. Six percent (6%) of Zemplar Capsules treated patients and 4% of placebo treated patients discontinued from clinical studies due to an adverse event. Adverse events occurring in the Zemplar Capsules group at a frequency of 2% or greater and more frequently than in the placebo group are presented in Table 1:
Table 1: Treatment-Emergent Adverse Events by Body System Occurring in ≥ 2% of Subjects in the Zemplar-Treated Group of Three, Double-Blind, Placebo-Controlled, Phase 3, CKD Stages 3 and 4 Studies; All Treated Patients
| Adverse Eventa | Number (%) of Subjects | |||
| Zemplar Capsules (n = 107) |
Placebo (n = 113) |
|||
| Overall | 88 | (82%) | 86 | (76%) |
| Ear and Labyrinth Disorders | ||||
| Vertigo | 5 | (4.7%) | 0 | (0.0%) |
| Gastrointestinal Disorders | ||||
| Abdominal Discomfort | 4 | (3.7%) | 1 | (0.9%) |
| Constipation | 4 | (3.7%) | 4 | (3.5%) |
| Diarrhea | 7 | (6.5%) | 5 | (4.4%) |
| Nausea | 6 | (5.6%) | 4 | (3.5%) |
| Vomiting | 5 | (4.7%) | 5 | (4.4%) |
| General Disorders and Administration Site Conditions | ||||
| Chest Pain | 3 | (2.8%) | 1 | (0.9%) |
| Edema | 6 | (5.6%) | 5 | (4.4%) |
| Pain | 4 | (3.7%) | 4 | (3.5%) |
| Immune System Disorders | ||||
| Hypersensitivity | 6 | (5.6%) | 2 | (1.8%) |
| Infections and Infestations | ||||
| Fungal Infection | 3 | (2.8%) | 0 | (0.0%) |
| Gastroenteritis | 3 | (2.8%) | 3 | (2.7%) |
| Infection | 3 | (2.8%) | 3 | (2.7%) |
| Sinusitis | 3 | (2.8%) | 1 | (0.9%) |
| Urinary Tract Infection | 3 | (2.8%) | 1 | (0.9%) |
| Viral Infection | 8 | (7.5%) | 8 | (7.1%) |
| Metabolism and Nutrition Disorders | ||||
| Dehydration | 3 | (2.8%) | 1 | (0.9%) |
| Musculoskeletal and Connective Tissue Disorders | ||||
| Arthritis | 5 | (4.7%) | 0 | (0.0%) |
| Back Pain | 3 | (2.8%) | 1 | (0.9%) |
| Muscle Spasms | 3 | (2.8%) | 0 | (0.0%) |
| Nervous System Disorders | ||||
| Dizziness | 5 | (4.7%) | 5 | (4.4%) |
| Headache | 5 | (4.7%) | 5 | (4.4%) |
| Syncope | 3 | (2.8%) | 1 | (0.9%) |
| Psychiatric Disorders | ||||
| Depression | 3 | (2.8%) | 0 | (0.0%) |
| Respiratory, Thoracic and Mediastinal Disorders | ||||
| Cough | 3 | (2.8%) | 2 | (1.8%) |
| Oropharyngeal Pain | 4 | (3.7%) | 0 | (0.0%) |
| Skin and Subcutaneous Tissue Disorders | ||||
| Pruritus | 3 | (2.8%) | 3 | (2.7%) |
| Rash | 4 | (3.7%) | 1 | (0.9%) |
| Skin Ulcer | 3 | (2.8%) | 0 | (0.0%) |
| Vascular Disorders | ||||
| Hypertension | 7 | (6.5%) | 4 | (3.5%) |
| Hypotension | 5 | (4.7%) | 3 | (2.7%) |
| a Includes only events more common in the Zemplar treatment group. | ||||
The following adverse reactions, with a causal relationship to Zemplar, occurred in < 2% of the Zemplar treated patients in the above double-blind, placebo-controlled clinical trial data set.
Gastrointestinal Disorders: Dry mouth
Investigations: Hepatic enzyme abnormal
Nervous System Disorders: Dysgeusia
Skin and Subcutaneous Tissue Disorders: Urticaria
CKD Stage 5
The safety of Zemplar Capsules has been evaluated in one 12-week, double-blind, placebo-controlled, multicenter clinical study involving 88 CKD Stage 5 patients. Sixty-one patients received Zemplar Capsules and 27 patients received placebo.
The proportion of patients who terminated prematurely from the study due to adverse events was 7% for Zemplar Capsules treated patients and 7% for placebo patients.
Adverse events occurring in the Zemplar Capsules group at a frequency of 2% or greater and more frequently than in the placebo group are as follows:
Table 2: Treatment-Emergent Adverse Events by Body System Occurring in ≥ 2% of Subjects in the Zemplar-Treated Group, Double-Blind, Placebo-Controlled, Phase 3, CKD Stage 5 Study; All Treated Patients
| Adverse Eventsa | Number (%) of Subjects | |||
| Zemplar Capsules (n=61) |
Placebo (n = 27) |
|||
| Overall | 43 | (70%) | 19 | (70%) |
| Gastrointestinal Disorders | ||||
| Constipation | 3 | (4.9%) | 0 | (0.0%) |
| Diarrhea | 7 | (11.5%) | 3 | (11.1%) |
| Vomiting | 4 | (6.6%) | 0 | (0.0%) |
| General Disorders and Administration Site Conditions | ||||
| Fatigue | 2 | (3.3%) | 0 | (0.0%) |
| Edema Peripheral | 2 | (3.3%) | 0 | (0.0%) |
| Infections and Infestations | ||||
| Nasopharyngitis | 5 | (8.2%) | 2 | (7.4%) |
| Peritonitis | 3 | (4.9%) | 0 | (0.0%) |
| Sinusitis | 2 | (3.3%) | 0 | (0.0%) |
| Urinary Tract Infection | 2 | (3.3%) | 0 | (0.0%) |
| Metabolism and Nutrition Disorders | ||||
| Fluid Overload | 3 | (4.9%) | 0 | (0.0%) |
| Hypoglycemia | 2 | (3.3%) | 0 | (0.0%) |
| Nervous System Disorders | ||||
| Dizziness | 4 | (6.6%) | 0 | (0.0%) |
| Headache | 2 | (3.3%) | 0 | (0.0%) |
| Psychiatric Disorders | ||||
| Anxiety | 2 | (3.3%) | 0 | (0.0%) |
| Insomnia | 3 | (4.9%) | 0 | (0.0%) |
| Renal and Urinary Disorders | ||||
| Renal Failure Chronic | 2 | (3.3%) | 0 | (0.0%) |
| a Includes only events more common in the Zemplar treatment group. | ||||
The following adverse reactions, with a causal relationship to Zemplar, occurred in < 2% of the Zemplar treated patients in the above double-blind, placebo-controlled clinical trial data set.
Gastrointestinal Disorders: Gastroesophageal reflux disease
Metabolism and Nutrition Disorders: Decreased appetite, hypercalcemia, hypocalcemia
Reproductive System and Breast Disorders: Breast tenderness
Skin and Subcutaneous Tissue Disorders: Acne
Postmarketing Experience
The following additional adverse reactions have been reported during post-approval use and post-approval clinical trials with the active ingredient in Zemplar capsules:
Immune System Disorders: Angioedema (including laryngeal edema)
Metabolism and Nutrition Disorders: Hypercalcemia
Investigations: Blood creatinine increased