adverse reactions
6 ADVERSE REACTIONS Most common adverse reactions (≥5%) are diarrhea, COVID-19, upper respiratory tract infection, depression, weight decreased, decreased appetite, nausea, fatigue, headache, vomiting, back pain, and dizziness. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Boehringer Ingelheim Pharmaceuticals, Inc. at (800) 542-6257 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 clinical trials of another drug and may not reflect the rates observed in practice. Adverse Reactions for Idiopathic Pulmonary Fibrosis The safety of JASCAYD was based on a randomized, placebo-controlled, double-blind trial (FIBRONEER-IPF), which included 1,177 adult patients with IPF who were randomized in a 1:1:1 ratio to receive JASCAYD 9 mg twice daily, JASCAYD 18 mg twice daily, or matching placebo. Patients received JASCAYD or placebo with or without background antifibrotic treatment (nintedanib or pirfenidone) for at least 52 weeks [see Clinical Studies (14.1) ] . The median duration of exposure was 14 months in each treatment arm. Discontinuation due to adverse reactions occurred more frequently in patients treated with JASCAYD (with or without background antifibrotic treatment) 18 mg (15%) and 9 mg (12%) compared to placebo (11%). The most frequent adverse reaction leading to discontinuation of JASCAYD 18 mg and 9 mg was diarrhea (6% and 2%, respectively). Table 1 lists the most common adverse reactions from the studied population with an incidence of greater than or equal to 5% in JASCAYD-treated patients and more common than the placebo group. Table 1 Adverse Reactions with JASCAYD with Incidence of ≥5% and More Common than Placebo in Patients 1 with IPF (FIBRONEER-IPF Trial) JASCAYD 18 mg BID n=392 JASCAYD 9 mg BID n=392 Placebo n=393 1 Studied population including patients who received JASCAYD with or without background antifibrotic treatment (nintedanib or pirfenidone) 2 Includes depression, depressed mood, depression rating scale score increased, suicidal ideation, adjustment disorder with depressed mood, depressive symptom BID: twice daily; COVID-19: infection with SARS-CoV-2 virus Diarrhea 42% 31% 17% COVID-19 13% 16% 12% Upper respiratory tract infection 13% 11% 10% Depression 2 12% 11% 10% Weight decreased 11% 10% 8% Decreased appetite 9% 9% 5% Nausea 8% 9% 7% Fatigue 7% 8% 6% Headache 7% 6% 5% Vomiting 6% 5% 5% Back pain 6% 5% 4% Dizziness 5% 6% 5% Specific Adverse Reactions of JASCAYD for IPF with or without Concomitant Use of Nintedanib or Pirfenidone Diarrhea Diarrhea was more common in patients using JASCAYD with concomitant nintedanib. In patients taking nintedanib, diarrhea occurred in 62%, 50%, and 28% of patients treated with JASCAYD 18 mg twice daily, JASCAYD 9 mg twice daily, and placebo, respectively. In patients using concomitant pirfenidone, diarrhea occurred in 24% and 8% of patients treated with JASCAYD 18 mg twice daily and placebo, respectively. In patients without concomitant antifibrotic treatment, diarrhea occurred in 26%, 17%, and 8% of patients using JASCAYD 18 mg twice daily, JASCAYD 9 mg twice daily, and placebo, respectively. Diarrhea was the most common adverse reaction associated with treatment discontinuation, and most common with JASCAYD used concomitantly with nintedanib: discontinuation occurred in 13%, 2%, and 1% of patients treated with JASCAYD 18 mg twice daily, JASCAYD 9 mg twice daily and placebo, respectively. No treatment discontinuations due to diarrhea occurred in patients treated with background pirfenidone and JASCAYD 18 mg twice daily or background pirfenidone with placebo. Diarrhea leading to treatment discontinuation occurred in 1% of patients treated with JASCAYD 18 mg twice daily and in no patients treated with JASCAYD 9 mg or placebo without concomitant antifibrotic treatment. In most patients treated with JASCAYD, diarrhea was of mild to moderate intensity and generally occurred within the first 3 months of treatment. Weight Decrease Weight decrease was most common in patients who received JASCAYD concomitantly with nintedanib in the studied population: in patients taking nintedanib, weight decrease occurred in 16%, 14%, and 12% of patients treated with JASCAYD 18 mg twice daily, JASCAYD 9 mg twice daily, and placebo, respectively. In patients using concomitant pirfenidone, weight decrease occurred in 6% and 5% of patients treated with JASCAYD 18 mg twice daily and placebo, respectively. In patients without background antifibrotic therapy, weight decrease occurred in 8%, 2%, and 6% of patients treated with JASCAYD 18 mg twice daily, JASCAYD 9 mg twice daily, and placebo, respectively. Decreased Appetite In patients taking nintedanib, decreased appetite occurred in 7%, 10%, and 4% in JASCAYD 18 mg twice daily, JASCAYD 9 mg twice daily, and placebo, respectively. In patients using concomitant pirfenidone, decreased appetite occurred in 13% and 10% of patients treated with JASCAYD 18 mg twice daily and placebo, respectively. In patients without concomitant antifibrotic treatment, decreased appetite occurred in 9%, 6%, and 0% of patients treated with JASCAYD 18 mg twice daily, JASCAYD 9 mg twice daily, and placebo, respectively. Less Common Adverse Reactions in IPF Less common adverse reactions in the IPF population following administration of JASCAYD included asthenia (5% JASCAYD 18 mg twice daily, 4% JASCAYD 9 mg twice daily, and 2% placebo), amylase increased (1% JASCAYD 18 mg twice daily, 1% JASCAYD 9 mg twice daily, and 0% placebo), and vasculitis (1% JASCAYD 18 mg twice daily, 1% JASCAYD 9 mg twice daily, and 0% placebo). Adverse Reactions for Progressive Pulmonary Fibrosis The safety of JASCAYD was based on a randomized, placebo-controlled, double-blind trial (FIBRONEER-ILD), in which 1,178 adult patients with PPF were randomized in a 1:1:1 ratio to receive JASCAYD 9 mg twice daily, JASCAYD 18 mg twice daily, or matching placebo. Patients received JASCAYD or placebo with or without background nintedanib treatment for at least 52 weeks [see Clinical Studies (14.2) ]. The median duration of exposure was 15 months in each treatment arm. The most common adverse reactions in patients with PPF treated with JASCAYD were generally consistent with those observed in patients with IPF. Specific Adverse Reactions of JASCAYD for PPF with or without Concomitant Use of Nintedanib Diarrhea Diarrhea was more common in patients using JASCAYD with concomitant nintedanib. In patients taking nintedanib, diarrhea occurred in 49%, 50%, and 37% of patients treated with JASCAYD 18 mg twice daily, JASCAYD 9 mg twice daily, and placebo, respectively. In patients without concomitant use of nintedanib, diarrhea occurred in 27%, 16%, and 16% of patients using JASCAYD 18 mg twice daily, JASCAYD 9 mg twice daily, and placebo, respectively. Diarrhea was the most common adverse reaction associated with treatment discontinuation, and most common with JASCAYD used concomitantly with nintedanib: discontinuation occurred in 4%, 3%, and 1% in patients treated with JASCAYD 18 mg twice daily, JASCAYD 9 mg twice daily, and placebo, respectively. Diarrhea leading to treatment discontinuation occurred in 1% of patients treated with JASCAYD 18 mg twice daily and in no patients treated with JASCAYD 9 mg or placebo without concomitant use of nintedanib. In most patients treated with JASCAYD, diarrhea was of mild to moderate intensity and generally occurred within the first 3 months of treatment. Weight Decrease Weight decrease was more common in patients who received JASCAYD concomitantly with nintedanib, which occurred in 12%, 10%, and 9% of patients treated with JASCAYD 18 mg twice daily, JASCAYD 9 mg twice daily, and placebo, respectively. In patients without concomitant use of nintedanib, weight decrease occurred in 13%, 8%, and 5% of patients treated with JASCAYD 18 mg twice daily, JASCAYD 9 mg twice daily, and placebo, respectively. Malignancies Among patients with PPF, neoplasms (benign, malignant, or unspecified) were reported in more patients with PPF treated with JASCAYD than placebo over the entire study duration of FIBRONEER-ILD (5% JASCAYD 18 mg, 5% JASCAYD 9 mg, and 3% placebo). Malignancies such as non-melanoma skin cancers and small cell lung cancer were observed in patients who received JASCAYD (basal cell carcinoma: JASCAYD 18 mg n=2 [1%] vs. JASCAYD 9 mg n=3 [1%] vs. placebo n=1 [0.3%]; squamous cell carcinoma of skin: JASCAYD 18 mg n=4 [1%] vs. JASCAYD 9 mg n=2 [0.5%] vs. placebo n=0; and small cell lung cancer: JASCAYD 18 mg n=4 [1%] vs. JASCAYD 9 mg and placebo n=0). Less Common Adverse Reactions in PPF Less common adverse reactions in the PPF population following administration of JASCAYD include atrial fibrillation (3% JASCAYD 18 mg twice daily, 2% JASCAYD 9 mg twice daily, and <1% placebo).