Randomized trial of the efficacy and safety of berotralstat (BCX7353) as an oral prophylactic therapy for hereditary angioedema: Results of APeX-2 through 48 weeks (part 2)

BACKGROUND: Berotralstat (BCX7353) is a recently approved, oral, once-daily kallikrein inhibitor for hereditary angioedema (HAE) prophylaxis. In the APeX-2 trial, berotralstat reduced HAE attack rates over 24 weeks, with a favorable safety and tolerability profile. OBJECTIVE: Evaluate berotralstat safety, tolerability, and effectiveness over 48 weeks. METHODS: APeX-2 is a phase 3, parallel-group, multicenter trial (NCT03485911) in patients with HAE due to C1 esterase inhibitor deficiency. Part 1 was double-blind and placebo-controlled, with patients randomized to 24 weeks of berotralstat 150 mg, 110 mg, or placebo. In part 2, patients continued berotralstat the same dose or, if initially randomized to placebo, were rerandomized to berotralstat 150 mg or 110 mg through weeks 24 to 48. The primary end point was safety and tolerability. RESULTS: One hundred eight patients received 1 or more doses of berotralstat in part 2. Treatment-emergent adverse events (TEAEs) occurred in 30 of 39 patients (77%) in the placebo group during part 1, and 25 of 34 patients (74%) re-randomized from placebo to berotralstat 110 mg or 150 mg in part 2, with drug-related TEAEs in 13 of 39 (33%), and 11 of 34 (32%) in the same groups. Most TEAEs were mild or moderate, with no serious drug-related TEAEs. The most common TEAEs were upper respiratory tract infections, abdominal pain, diarrhea, and vomiting. Mean (±standard error of the mean) monthly attack rates at baseline and week 48 were 3.06 (±0.25) and 1.06 (±0.25) in the berotralstat 150mg 48-week group and 2.97 (±0.21) and 1.35 (±0.33) in the berotralstat 110mg 48-week group. CONCLUSIONS: The safety, tolerability, and effectiveness of berotralstat were maintained over 48 weeks of treatment

Fundamentación lógica de la física

CARNAP, Rudolf. Fundamentación lógica de la física. Buenos Aires, Editorial Sudamericana, 1969. 394 p

Tests para selección de personal

GUION, Robert. N. Tests para selección de personal. Madrid, Ediciones Riap, 1969. 774 p. Tradução espanhola de Personnel testing. New York, MacGraw-Hill

Oral once-daily berotralstat for the prevention of hereditary angioedema attacks: A randomized, double-blind, placebo-controlled phase 3 trial

BACKGROUND: Berotralstat (BCX7353) is an oral, once-daily inhibitor of plasma kallikrein in development for the prophylaxis of hereditary angioedema (HAE) attacks. OBJECTIVE: Our aim was to determine the efficacy, safety, and tolerability of berotralstat in patients with HAE over a 24-week treatment period (the phase 3 APeX-2 trial). METHODS: APeX-2 was a double-blind, parallel-group study that randomized patients at 40 sites in 11 countries 1:1:1 to receive once-daily berotralstat in a dose of 110 mg or 150 mg or placebo (Clinicaltrials.gov identifier NCT03485911). Patients aged 12 years or older with HAE due to C1 inhibitor deficiency and at least 2 investigator-confirmed HAE attacks in the first 56 days of a prospective run-in period were eligible. The primary efficacy end point was the rate of investigator-confirmed HAE attacks during the 24-week treatment period. RESULTS: A total of 121 patients were randomized; 120 of them received at least 1 dose of the study drug (n = 41, 40, and 39 in the 110-mg dose of berotralstat, 150-mg of dose berotralstat, and placebo groups, respectively). Berotralstat demonstrated a significant reduction in attack rate at both 110 mg (1.65 attacks per month; P = .024) and 150 mg (1.31 attacks per month; P \u3c .001) relative to placebo (2.35 attacks per month). The most frequent treatment-emergent adverse events that occurred more with berotralstat than with placebo were abdominal pain, vomiting, diarrhea, and back pain. No drug-related serious treatment-emergent adverse events occurred. CONCLUSION: Both the 110-mg and 150-mg doses of berotralstat reduced HAE attack rates compared with placebo and were safe and generally well tolerated. The most favorable benefit-to-risk profile was observed at a dose of 150 mg per day

Keep the cat, change the care pathway: A transformational approach to managing Fel d 1, the major cat allergen

BACKGROUND: Allergies to cats are the most common animal-origin allergy, and affect approximately 1 in 5 adults worldwide. The prevalence of allergy to furry animals has been increasing, and allergy to cats is a major risk factor for the development of asthma and rhinitis. The diagnosis of cat allergy is now well established. The exact significance of component-resolved diagnosis in the diagnosis of cat allergy remains to be fully understood. Allergen avoidance is effective but often has a psychologic impact. Allergen immunotherapy is not well demonstrated. There is a need for innovative approaches to better manage cat allergens. Next-generation care pathways for asthma and rhinitis will define the place of cat allergen avoidance. METHODS AND RESULTS: This manuscript, based on content presented at the European Academy of Allergy and Clinical Immunology Congress 2019, provides information on the prevalence and impact of cat allergies and the molecular biology of Fel d 1, the major cat allergen. DISCUSSION: The authors present the scientific basis of a novel care pathway that utilizes anti-Fel d 1 IgY antibodies to safely and effectively neutralize Fel d 1 after its production by the cat but before human exposure. CONCLUSION: Efficacy of a feline diet with an egg product ingredient containing anti-Fel d 1 IgY antibodies was demonstrated in vitro, ex vivo, and in vivo, and further validated by a pilot exposure study involving cat-allergic human participants

Once-daily oral berotralstat for long-term prophylaxis of hereditary angioedema: The open-label extension of the APeX-2 randomized trial

BACKGROUND: Berotralstat is a first-line, once-daily oral plasma kallikrein inhibitor approved for prophylaxis of hereditary angioedema (HAE) attacks in patients 12 years or older. OBJECTIVE: This analysis examined the safety and effectiveness of long-term prophylaxis with berotralstat. METHODS: APeX-2 was a phase 3, parallel-group, multicenter trial in patients with HAE caused by C1-inhibitor deficiency (NCT03485911). Part 1 was a randomized, double-blind, placebo-controlled evaluation of 150 and 110 mg of berotralstat over 24 weeks. In part 2, berotralstat-treated patients continued the same treatment, and placebo-treated patients were re-randomized to 150 or 110 mg of berotralstat for 24 weeks. In part 3, all patients were treated with open-label berotralstat at 150 mg, which could be continued for up to an additional 4 years. In part 3, the primary endpoint was long-term safety and tolerability. Secondary endpoints included HAE attack rates and quality of life (QoL). RESULTS: Eighty-one patients entered part 3. Treatment-emergent adverse events (TEAEs) occurred in 82.7% of patients, with most being mild or moderate in severity. The most common TEAEs were nasopharyngitis, urinary tract infection, abdominal pain, arthralgia, coronavirus infection, and diarrhea. Drug-related TEAEs occurred in 14.8% of patients, but none were serious. For patients who completed 96 weeks of berotralstat treatment (n = 70), the mean (standard error) change in attack rate from baseline was -2.21 (0.20) attacks/mo. Clinically meaningful improvements in QoL were also observed, with the largest improvements in the functioning domain. CONCLUSION: Berotralstat was generally well tolerated, provided rapid and sustained reductions in HAE attacks and improved QoL over 96 weeks

Liberdade para aprender

Rogers, Carl R. Liberdade para aprender. Minas Gerais, Entrelivros, 1971. 331 p

Modificação do comportamento e sociedade controlada

Robert L. Geiser. Modificação do comportamento e sociedade controlada. Trad. Zahar, Rio de Janeiro, 1977. 168p