Donanemab immunogenicity in participants with early symptomatic Alzheimer's disease.

Introduction: Donanemab is an immunoglobulin G1 antibody that targets an N-terminal truncated form of amyloid beta present in mature plaques. Treatment-emergent (TE) anti-drug antibodies (ADAs) were quantified in donanemab-treated participants from two pivotal clinical trials, and effects of TE ADAs on donanemab pharmacokinetics, efficacy, and safety were assessed.

Methods: Data were pooled from the phase 2 TRAILBLAZER-ALZ (NCT03367403) and phase 3 TRAILBLAZER-ALZ 2 trials (NCT04437511).

Tirzepatide Immunogenicity on Pharmacokinetics, Efficacy, and Safety: Analysis of Data From Phase 3 Studies.

Context: Antidrug antibodies (ADA) can potentially affect drug pharmacokinetics, safety, and efficacy.

Objective: This work aimed to evaluate treatment-emergent (TE) ADA in tirzepatide (TZP)-treated participants across 7 phase 3 trials and their potential effect on pharmacokinetics, efficacy, and safety.

Methods: ADA were assessed at baseline and throughout the study until end point, defined as week 40 (SURPASS-1, -2, and -5) or week 52 (SURPASS-3, -4, Japan-Mono, and Japan-Combo).

Assessment of immunogenicity from galcanezumab phase 3 trials in patients with episodic or chronic migraine.

Background: This analysis characterizes the immunogenicity profile of galcanezumab, a humanized monoclonal antibody that selectively binds calcitonin gene-related peptide and inhibits its activity, in phase 3 migraine trials.

Methods: Immunogenicity data were analyzed from baseline and double-blind, placebo-controlled phases of the 3-month chronic migraine study REGAIN, the 6-month episodic migraine studies EVOLVE-1 and EVOLVE-2, and from baseline and open-label phases of the 12-month chronic and episodic migraine Study CGAJ. The incidence of baseline antidrug antibodies, treatment-emergent antidrug antibodies, neutralizing antidrug antibodies, and the effect of antidrug antibody titer on pharmacokinetics and pharmacodynamics were assessed.

What is clearance worth? Patients' stated risk tolerance for psoriasis treatments.

Purpose: The purpose of this study was to provide quantitative evidence of patients' tolerance for therapeutic risks associated with psoriasis treatments that could offer psoriasis improvements beyond the PASI 75 benchmark.

Materials And Methods: We used a discrete-choice experiment in which respondents chose between competing psoriasis treatments characterized by benefits (i.e.

Assessment of Pancreas Safety in the Development Program of Once-Weekly GLP-1 Receptor Agonist Dulaglutide.

Objective: To assess the risk of acute pancreatitis during treatment with glucagon-like peptide 1 receptor agonist dulaglutide, placebo, and active comparators across phase 2/3 dulaglutide trials.

Research Design And Methods: A total of 6,005 patients with type 2 diabetes participated (dulaglutide group = 4,006 [dose range 0.1-3.

Effective Partnering in Conducting Benefit-Risk Patient Preference Studies: Perspectives From a Patient Advocacy Organization, a Pharmaceutical Company, and Academic Stated-Preference Researchers.

Background: Formal incorporation of patients' perspectives is becoming increasingly important in medical product development and decision making. This article shares practical advice regarding how patient advocacy organizations, the pharmaceutical industry, and academic experts in stated-preference research can effectively partner on benefit-risk patient preference studies.

Methods: The authors partnered on a benefit-risk patient preference study related to the treatment of psoriasis.

Implementation of Structured Benefit-Risk Assessments in Marketing Authorization Applications: Lessons Learned.

Background: A recent publication from Eli Lilly and Company provided guidance on incorporation of a structured benefit-risk assessment framework into Section 2.5.6 of the Clinical Overview of marketing authorization applications.

Effects of once-weekly dulaglutide on kidney function in patients with type 2 diabetes in phase II and III clinical trials.

Dulaglutide is a once-weekly glucagon-like peptide-1 receptor agonist approved for the treatment of type 2 diabetes (T2D). Integrated data from 9 phase II and III trials in people with T2D (N = 6005) were used to evaluate the effects of dulaglutide on estimated glomerular filtration rate (eGFR [Chronic Kidney Disease Epidemiology Collaboration]), urine albumin-to-creatinine ratio (UACR) and kidney adverse events (AEs). No significant differences in eGFR were observed during treatment for dulaglutide vs placebo, active comparators or insulin glargine (mean ± standard deviation values: dulaglutide vs placebo: 87.

Genomic imprinting in Turner syndrome: effects on response to growth hormone and on risk of sensorineural hearing loss.

Context: Evidence exists for X-linked parent-of-origin effects in Turner syndrome, because phenotypic and cognitive profiles differ between 45,X(maternal) and 45,X(paternal) individuals.

Objective And Design: We evaluated the parent-of-origin effect of the intact X chromosome on spontaneous growth, GH-stimulated height gain, and frequency of sensorineural hearing loss in 54 subjects with Turner syndrome recruited from a Canadian randomized, controlled trial of GH supplementation to adult height.

Methods And Results: Microsatellite analyses revealed that 72% of nonmosaic 45,X subjects retained an X(maternal), whereas 86% of nonmosaic 46,X,i(Xq) subjects carried an intact X(paternal).

Efficacy and safety of oral tadalafil in the treatment of men in Canada with erectile dysfunction: a randomized, double-blind, parallel, placebo-controlled clinical trial.

Introduction: Erectile dysfunction (ED) is a highly prevalent, often undertreated condition.

Aim: This 12-week, double-blind, parallel, placebo-controlled study was conducted at 25 sites in Canada to evaluate the efficacy and safety of oral tadalafil, a phosphodiesterase type 5 inhibitor, for the treatment of ED.

Methods: Men with ED of organic, psychogenic, or mixed etiology were stratified by baseline ED severity then randomly assigned to placebo (N = 50), tadalafil 10 mg (N = 103), or tadalafil 20 mg (N = 100), taken as needed (maximum, once daily).

Efficacy of tadalafil for the treatment of erectile dysfunction at 24 and 36 hours after dosing: a randomized controlled trial.

Objectives: To examine the therapeutic effects of tadalafil on erectile dysfunction (ED) at 24 and 36 hours after dosing.

Methods: A multicenter, randomized, double-blind, placebo-controlled, parallel-group study of 348 men (mean age 57 years) with ED was conducted in Europe and the United States. Patients were stratified by baseline severity of ED using the Erectile Function domain score of the International Index of Erectile Function and then randomly allocated within the severity group to receive tadalafil 20 mg (n = 175) or placebo (n = 173).

Effects of tadalafil on erectile dysfunction in men with diabetes.

Objective: To evaluate the efficacy and safety of tadalafil taken as needed before sexual activity by men with diabetes and erectile dysfunction (ED).

Research Design And Methods: Men with type 1 or type 2 diabetes and a minimum 3-month history of ED were randomly allocated to one of three groups: placebo (n = 71), tadalafil 10 mg (n = 73), or tadalafil 20 mg (n = 72) taken up to once daily for 12 weeks. Changes from baseline in mean scores on the erectile function domain of the International Index of Erectile Function (IIEF) and changes from baseline in the proportion of "yes" responses to question 2, "Were you able to penetrate?," and 3, "Were you able to complete intercourse?," of the Sexual Encounter Profile were coprimary outcome measures.

Efficacy and safety of tadalafil for the treatment of erectile dysfunction: results of integrated analyses.

Purpose: We conducted integrated analyses of the efficacy and safety of tadalafil, a potent, selective phosphodiesterase 5 inhibitor, for the treatment of erectile dysfunction.

Materials And Methods: A total of 1,112 men with a mean age of 59 years (range 22 to 82) and mild to severe erectile dysfunction of various etiologies were randomized to placebo or tadalafil, taken as needed without food or alcohol restrictions, at fixed daily doses of 2.5 mg, 5 mg, 10 mg, or 20 mg up to a maximum of once daily [DOSAGE ERROR CORRECTED] in 5 randomized, double-blind, placebo controlled trials lasting 12 weeks.

Growth hormone and low dose estrogen in Turner syndrome: results of a United States multi-center trial to near-final height.

A cardinal clinical feature of Turner syndrome (TS) is linear growth failure resulting in extreme short stature: the median adult height of untreated women with TS is 143 cm, 20 cm (8 in.) below that of the general female population. In the largest multicenter, randomized, long-term, dose-response study conducted in the United States, 232 subjects with TS received either 0.