Haiyuan Zhu

Karuna Therapeutics

Poisson and negative binomial models are frequently used to analyze count data in clinical trials. While several sample size calculation methods have recently been developed for superiority tests for these two models, similar methods for non-inferiority and equivalence tests are not available. When a non-inferiority or equivalence trial is designed...

Background Roflumilast, a once-daily, selective phosphodiesterase-4 inhibitor, reduces the risk of COPD exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations. The RE²SPOND study is examining whether roflumilast, when added to an inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) fixed-dos...

The number of patient-years needed to treat (NPYNT), also called the event-based number needed to treat, to avoid one additional exacerbation has been reported in recently published respiratory trials, but the confidence intervals are not routinely reported. The challenge of constructing confidence intervals for NPYNT is due to the fact that exacer...

Negative binomial model has been increasingly used to model the count data in recent clinical trials. It is frequently chosen over Poisson model in cases of overdispersed count data that are commonly seen in clinical trials. One of the challenges of applying negative binomial model in clinical trial design is the sample size estimation. In practice...

This post-hoc analysis examined the impact of roflumilast on chronic obstructive pulmonary disease (COPD) exacerbations and lung function in patients with COPD who received concomitant long-acting β2-agonists (LABA) with or without prior inhaled corticosteroid (ICS) and the influence of various demographic and clinical characteristics on these outc...

Background: Sarcopenia, the age-related loss of muscle mass [defined as appendicular LBM/Height2 (aLBM/ht2) below peak value by>1SD], strength and function, is a major contributing factor to frailty in the elderly. MK-0773 is a selective androgen receptor modulator designed to improve muscle function while minimizing effects on other tissues. Obj...

Background: Evaluation of cardiovascular safety for new therapies for COPD is important because of a high prevalence of cardiac comorbidities in the COPD population. Hence, we evaluated the effects of roflumilast, a novel oral phosphodiesterase 4 inhibitor developed for the treatment and prevention of COPD exacerbations, on major adverse cardiovas...

Neurokinin-1 receptor dependent mechanisms may regulate urinary frequency and urgency. We conducted this study to assess the efficacy and tolerability of the neurokinin-1 receptor antagonist serlopitant vs placebo or tolterodine in patients with overactive bladder. This randomized, double-blind, 69-center trial enrolled adults with overactive bladd...

MK-0493 is a novel, potent, and selective agonist of the melanocortin receptor 4 (MC4R), one of the best-validated genetic targets and considered one of the most promising for the development of antiobesity therapeutics. An ad libitum energy-intake model was qualified with excellent reproducibility: the geometric mean ratio (GMR) with 95% confidenc...

The gastrointestinal peptide hormone, peptide YY(3-36) (PYY(3-36)), is implicated to be a postprandial satiety factor. The aim of this study is to assess the safety, tolerability, and efficacy of intranasal PYY(3-36) to induce weight loss in obese patients. The study was designed as a randomized, 2-wk, single-blind placebo run-in followed by a 12-w...

The objective of these studies was to evaluate the pharmacokinetics and pharmacodynamics of MK-0767, a prototypical dual peroxisome proliferator-activated receptor (PPAR) alpha/gamma agonist, following administration of single and multiple oral doses in healthy male subjects. The first study was a double-blind, randomised, placebo-controlled, alter...

An analysis was performed to compare preliminary pharmacokinetics (PK) of MK-0767, a dual PPAR|[alpha]|/|[gamma]| agonist, between Japanese and non-Japanese populations after single and multiple oral doses of MK-0767. The PK data from available MK-0767 Phase I studies in a non-Japanese population (5 studies) were pooled (single dose and multiple do...

We consider the class of saturated main effect plans for the 2k factorial. With these saturated designs, the overall mean and all main effects can be unbiasedly estimated provided that there are no interactions. However, there is no way to estimate the error variance with such designs. Because of this and other reasons, we like to add some addition...

P-Glycoprotein (Pgp) associated multidrug-resistance (MDR) is a significant factor that can lead to the failure of cancer chemotherapy. Several new tropane alkaloid aromatic esters obtained from extracts of Erythroxylum pervillei Baillon (Erythroxylaceae) (1-8) and Erythroxylum rotundifolium Lunan (Erythroxylaceae) (9-12) by means of bioassay-direc...

Thesis (Ph. D.)--University of Illinois at Chicago, 2002. Vita. Includes bibliographical references (leaves 95-98).