Apremilastside effects

The following adverse reactions are described elsewhere in the labeling: Hypersensitivity Diarrhea, Nausea, and Vomiting Depression Weight Decrease Drug Interactions Psoriatic Arthritis: The most common adverse reactions (≥ 5%) are diarrhea, nausea, and headache Plaque Psoriasis: The most common adverse reactions (≥ 5%) are diarrhea, nausea, upper respiratory tract infection, and headache, including tension headache Behçet's Disease: The most common adverse reactions (≥ 10%) are diarrhea, nausea, headache, and upper respiratory tract infection To report SUSPECTED ADVERSE REACTIONS, contact Amgen Inc. at 1-800-77-AMGEN (1-800-772-6436) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical

Trials 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. Psoriatic Arthritis Clinical Trials OTEZLA was evaluated in three multicenter, randomized, double-blind, placebo-controlled trials (PsA-1, PsA-2, and PsA-3) of similar design in adult subjects with active psoriatic arthritis. Across the three trials, there were 1493 subjects randomized equally to placebo, OTEZLA 20 mg twice daily or OTEZLA 30 mg twice daily. Titration was used over the first 5 days. Placebo subjects whose tender and swollen joint counts had not improved by at least 20% were re-randomized 1:1 in a blinded fashion to either OTEZLA 20 mg twice daily or 30 mg twice daily at week 16 while OTEZLA subjects remained on their initial treatment. Subjects ranged in age from 18 to 83 years, with an overall median age of 51 years. The majority of the most common adverse reactions presented in Table 3 occurred within the first 2 weeks of treatment and tended to resolve over time with continued dosing. Diarrhea, headache, and nausea were the most commonly reported adverse reactions. The most common adverse reactions leading to discontinuation for subjects taking OTEZLA were nausea (1.8%), diarrhea (1.8%), and headache (1.2%). The proportion of subjects with psoriatic arthritis who discontinued treatment due to any adverse reaction was 4.6% for subjects taking OTEZLA 30 mg twice daily and 1.2% for placebo-treated subjects. Table 3. Adverse Reactions Reported in ≥ 2% of Adult Subjects with Active Psoriatic Arthritis on OTEZLA 30 mg Twice Daily and ≥ 1% than That Observed in Subjects on Placebo up to Day 112 (Week 16) Placebo OTEZLA 30 mg BID BID = twice daily. Adverse Reactions Day 1 to 5 (N = 495) n (%) n (%) indicates number of subjects and percent. Day 6 to Day 112 (N = 490) n (%) Day 1 to 5 (N = 497) n (%) Day 6 to Day 112 (N = 493) n (%) Diarrhea Of the reported gastrointestinal adverse reactions, 1 subject experienced a serious adverse reaction of nausea and vomiting in OTEZLA 30 mg twice daily; 1 subject treated with OTEZLA 20 mg twice daily experienced a serious adverse reaction of diarrhea; 1 subject treated with OTEZLA 30 mg twice daily experienced a serious adverse reaction of headache. 6 8 46 38 Nausea 7 15 37 44 Headache 9 11 24 29 Upper respiratory tract infection Of the reported adverse drug reactions none were serious. 3 9 3 19 Vomiting 2 2 4 16 Nasopharyngitis 1 8 1 13 Abdominal pain upper 0 1 3 10 Moderate to Severe Plaque Psoriasis Clinical Trials Adverse Reactions from Clinical Trials in Adults The safety of OTEZLA was assessed in 1426 subjects in three randomized, double-blind, placebo-controlled trials in adult subjects with moderate to severe plaque psoriasis who were candidates for phototherapy or systemic therapy. Subjects were randomized to receive OTEZLA 30 mg twice daily or placebo twice daily. Titration was used over the first 5 days. Subjects ranged in age from 18 to 83 years, with an overall median age of 46 years. Diarrhea, nausea, and upper respiratory tract infection were the most commonly reported adverse reactions (see Table 4 ). The most common adverse reactions leading to discontinuation for subjects taking OTEZLA were nausea (1.6%), diarrhea (1.0%), and headache (0.8%). The proportion of subjects with plaque psoriasis who discontinued treatment due to any adverse reaction was 6.1% for subjects treated with OTEZLA 30 mg twice daily and 4.1% for placebo-treated subjects. Table 4. Adverse Reactions Reported in ≥ 1% of Adult Subjects with Moderate to Severe Plaque Psoriasis on OTEZLA and With Greater Frequency Than in Subjects on Placebo up to Day 112 (Week 16) Adverse Reactions Placebo (N = 506) n (%) OTEZLA 30 mg BID BID = twice daily. (N = 920) n (%) Diarrhea 32 160 Nausea 35 155 Upper respiratory tract infection 31 84 Tension headache 21 75 Headache 19 55 Abdominal pain Two subjects treated with OTEZLA experienced serious adverse reaction of abdominal pain. 11 39 Vomiting 8 35 Fatigue 9 29 Dyspepsia 6 29 Decreased appetite 5 26 Insomnia 4 21 Back pain 4 20 Migraine 5 19 Frequent bowel movements 1 17 Depression 2 12 Bronchitis 2 12 Tooth abscess 0 10 Folliculitis 0 9 Sinus headache 0 9 Severe worsening of psoriasis (rebound) occurred in 0.3% (4/1184) subjects following discontinuation of treatment with OTEZLA. OTEZLA was evaluated in a Phase 3, multicenter, randomized, placebo-controlled trial (PSOR-3) in adults with moderate to severe plaque psoriasis of the scalp. A total of 302 subjects were randomized to receive OTEZLA 30 mg twice daily or placebo twice daily. The most commonly reported adverse reactions that occurred at a higher rate in the OTEZLA group than in the placebo group were: diarrhea (31% vs. 11%), nausea (22% vs. 6%), headache (12% vs. 5%), and vomiting (6% vs. 2%). The proportion of subjects who discontinued treatment because of any adverse reaction during the 16-week placebo-controlled period of the trial was 6% for subjects who received OTEZLA 30 mg twice daily and 3% for subjects who received placebo. Gastrointestinal adverse reactions that led to discontinuation of treatment were diarrhea (3% vs. 0%), nausea (1.5% vs. 1%), and vomiting (1.5% vs. 0%) in the OTEZLA group compared to placebo. OTEZLA was evaluated in a Phase 3, multicenter, randomized, placebo-controlled trial (PSOR-5) in adults with moderate to severe plaque psoriasis of the genital area. A total of 289 subjects were randomized to receive OTEZLA 30 mg twice daily or placebo twice daily. Overall, the safety profile observed in the OTEZLA group during the placebo-controlled phase was consistent with the safety profile previously established in adult subjects with moderate to severe plaque psoriasis. Adverse Reactions from Clinical Trials in Pediatric Subjects 6 to 17 Years of Age OTEZLA was evaluated in a Phase 3, multicenter, randomized, placebo-controlled trial (PSOR-6) in pediatric subjects 6 to 17 years of age with moderate to severe plaque psoriasis. A total of 245 subjects were randomized to receive OTEZLA (163 subjects, at a dosage of 20 mg twice daily or 30 mg twice daily, based on body weight) or placebo (82 subjects) twice daily during the 16-week placebo-controlled phase of the trial. The trial also included a 36-week extension phase during which all subjects received OTEZLA 20 mg or 30 mg twice daily. Overall, the safety profile observed in pediatric subjects treated with OTEZLA during the study was consistent with the safety profile established in adult subjects with moderate to severe plaque psoriasis. Mild to Moderate Plaque Psoriasis Clinical Trial in Adults OTEZLA was evaluated in a Phase 3, multicenter, randomized, placebo-controlled trial (PSOR-4) in adult subjects with mild to moderate plaque psoriasis. A total of 595 subjects were randomized to receive OTEZLA 30 mg twice daily (297 subjects) or placebo twice daily (298 subjects) during the placebo-controlled phase of the trial. The trial also included an open label extension phase during which all subjects received OTEZLA 30 mg twice daily. Overall, the safety profile observed in the OTEZLA group during the placebo-controlled phase was consistent with the safety profile previously established in adult subjects with moderate to severe plaque psoriasis. Behçet's Disease Clinical Trials OTEZLA was evaluated in a Phase 3, multicenter, randomized, placebo-controlled trial (BCT-002) in adult subjects with Behçet's Disease (BD) with active oral ulcers. A total of 207 subjects were randomized to receive OTEZLA 30 mg twice daily or placebo twice daily. Titration was used over the first 5 days. After Week 12, all subjects received treatment with OTEZLA 30 mg twice daily. Subjects ranged in age from 19 to 72, with a mean age of 40 years. Diarrhea, nausea, headache, and upper respiratory tract infection were the most commonly reported adverse reactions (see Table 5 ). The proportion of subjects with BD who discontinued treatment due to any adverse reaction during the placebo-controlled period of the trial, was 2.9% for subjects treated with OTEZLA 30 mg twice daily and 4.9% for placebo-treated subjects. Table 5. Adverse Reactions Reported in ≥ 5% of Adult Subjects with BD with Active Oral Ulcers on OTEZLA and with at Least 1% Greater Frequency than Subjects on Placebo up to Week 12 Adverse Reactions Placebo (N = 103) n (%) OTEZLA 30 mg twice daily (N = 104) n (%) Diarrhea There were no serious adverse reactions of diarrhea, nausea or vomiting. 21 43 Nausea 11 20 Headache 11 15 Upper respiratory tract infection 5 12 Abdominal pain upper 2 9 Vomiting 2 9 Back pain 6 8 Viral upper respiratory tract infection 5 7 Arthralgia 3 6 Other adverse reactions reported in subjects on OTEZLA in psoriatic arthritis, plaque psoriasis, and Behçet's Disease clinical trials are: Gastrointestinal Disorders: Gastroesophageal reflux disease Immune System Disorders: Hypersensitivity Investigations: Weight decrease Metabolism and Nutrition Disorders: Decreased appetite One subject treated with OTEZLA 30 mg twice daily experienced a serious adverse reaction.

Nervous System Disorders: Migraine Respiratory, Thoracic, and Mediastinal Disorders: Cough Skin and Subcutaneous Tissue Disorders: Rash