BLEEDING PATTERNS WITH USE OF AN ORAL CONTRACEPTIVE CONTAINING ESTETROL AND DROSPIRENONE: POOLED ANALYSIS OF PHASE-3 CLINICAL TRIALS

An adjuvanted recombinant zoster vaccine (RZV) is licensed for the prevention of herpes zoster. This paper reviews its safety and reactogenicity. A pooled analysis of two pivotal randomized Phase-3 trials (NCT01165177, NCT01165229) in adults ⩾50 years found that more solicited adverse events (AEs) were reported with RZV than placebo. Injection site pain was the most common solicited AE (RZV: 78.0% participants; placebo: 10.9%). Grade-3 pain occurred in 6.4% of RZV and 0.3% of placebo recipients. Myalgia, fatigue, and headache were the most commonly reported general solicited AEs (RZV: 44.7%, 44.5%, and 37.7%, respectively; placebo: 11.7%, 16.5%, and 15.5%, respectively). Most symptoms were mild to moderate in intensity with a median duration of 2–3 days. The intensity of reactogenicity symptoms did not differ substantially after the first and second vaccine doses. The pooled analysis of the pivotal Phase-3 trials did not identify any clinically relevant differences in the overall incidence of serious adverse events (SAEs), fatal AEs or potential immune-mediated diseases (pIMDs) between RZV and placebo. Reactogenicity in five studies of immunocompromised patients ⩾18 years (autologous stem cell transplant, human immunodeficiency virus, solid tumors, hematological malignancies, and renal transplant; NCT01610414, NCT01165203, NCT01798056, NCT01767467, and NCT02058589) was consistent with that observed in the pivotal Phase-3 trials. There were no clinically relevant differences between RZV and placebo in the immunocompromised populations with regard to overall incidence of SAEs, fatal AEs, pIMDs, or AEs related to patients’ underlying condition. Post-marketing surveillance found that the most commonly reported AEs were consistent with the reactogenicity profile of the vaccine in clinical trials. Overall, the clinical safety data for RZV are reassuring. [Formula: see text]

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A Pooled Analysis of Two Phase 3 Clinical Trials of Dalfampridine in Patients with Multiple Sclerosis

International Journal of MS Care ◽

10.7224/1537-2073.2013-023 ◽

2014 ◽

Vol 16 (3) ◽

pp. 153-160 ◽

Cited By ~ 17

Author(s):

Andrew D. Goodman ◽

Theodore R. Brown ◽

Randall T. Schapiro ◽

Michael Klingler ◽

Ron Cohen ◽

...

Keyword(s):

Multiple Sclerosis ◽

Clinical Trials ◽

Clinical Characteristics ◽

Walking Speed ◽

Pooled Analysis ◽

Responder Rate ◽

Phase 3 ◽

Two Phase ◽

Pooled Data ◽

The Individual

Background: Two phase 3 clinical trials demonstrated that dalfampridine extended-release 10-mg tablets (D-ER), twice daily, significantly improved walking relative to placebo in patients with multiple sclerosis (MS). The objective of this study was to evaluate the efficacy and safety of D-ER in patients with MS using pooled data from the two phase 3 trials. Methods: Data were pooled from the two trials, and D-ER was compared with placebo for timed-walk responder rate, changes in walking speed, and the 12-item Multiple Sclerosis Walking Scale (MSWS-12). Response rates were evaluated with respect to demographic and clinical characteristics. Results: D-ER had a significantly higher proportion of timed-walk responders relative to placebo (37.6% vs. 8.9%; P < .0001). The responder rate was independent of age, gender, race, body-mass index, type of MS, duration of MS, baseline Expanded Disability Status Scale score, baseline walking speed, and concomitant use of immunomodulatory therapies. Significant improvements were observed in walking speed and in MSWS-12 score for the pooled D-ER group compared with placebo. The safety profile was consistent with the individual studies; no new safety or tolerability concerns were identified. Conclusions: D-ER demonstrated efficacy for the improvement of walking in patients with MS; response was independent of demographic and clinical characteristics.

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Objective Cough Frequency with Gefapixant in Chronic Cough: A Pooled Analysis of Two Phase 3 Randomized, Controlled Clinical Trials (COUGH-1 and COUGH-2)

10.1164/ajrccm-conference.2021.203.1_meetingabstracts.a2353 ◽

2021 ◽

Author(s):

J. Smith ◽

A.H. Morice ◽

L. Mcgarvey ◽

I.D. Pavord ◽

S.S. Birring ◽

...

Keyword(s):

Clinical Trials ◽

Chronic Cough ◽

Pooled Analysis ◽

Controlled Clinical Trials ◽

Phase 3 ◽

Two Phase ◽

Randomized Controlled Clinical Trials ◽

Randomized Controlled ◽

Cough Frequency

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Bempedoic Acid Efficacy and Safety in High CVD Risk Patients Treated With or Without Ezetimibe: Pooled Analysis of 4 Phase 3 Clinical Trials†

Journal of Clinical Lipidology ◽

10.1016/j.jacl.2020.05.044 ◽

2020 ◽

Vol 14 (4) ◽

pp. 569-570

Author(s):

Alberico Catapano ◽

Harold Bays ◽

Maciej Banach ◽

P. Duell ◽

Ulrich Laufs ◽

...

Keyword(s):

Clinical Trials ◽

Pooled Analysis ◽

Efficacy And Safety ◽

Cvd Risk ◽

Phase 3 ◽

Risk Patients

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Abstract 14248: Efficacy and Safety of Bempedoic Acid in Patients Who Cannot Tolerate Statins: Pooled Analysis of 4 Phase 3 Clinical Trials

Circulation ◽

10.1161/circ.142.suppl_3.14248 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Ulrich Laufs ◽

Maciej Banach ◽

Harold E Bays ◽

Alberico L Catapano ◽

P Barton Duell ◽

...

Keyword(s):

Clinical Trials ◽

Adverse Events ◽

Pooled Analysis ◽

Lipid Lowering ◽

Drug Discontinuation ◽

Lipid Lowering Therapy ◽

Efficacy And Safety ◽

Statin Intolerance ◽

Phase 3 ◽

Additional Information

Introduction: Some patients cannot tolerate statins mainly because of statin-associated muscle symptoms (SAMS). Bempedoic acid (BA) is a prodrug activated in the liver and not in skeletal muscle. BA has been shown to significantly lower LDL-C by a mean of ~18% in patients receiving background maximally tolerated statins and a mean of ~25% in patients with statin intolerance. Objective: Determine efficacy and safety of BA in statin-intolerant patients receiving no background statin therapy across 4 phase 3 clinical trials. Methods: Data were pooled from 4 randomized (2:1), placebo-controlled studies evaluating oral BA 180 mg once daily vs placebo for 12 to 52 weeks. Primary efficacy endpoint was LDL-C % change from baseline to week 12. Safety assessments included treatment-emergent adverse events (TEAEs), adverse events of special interest (AESI), and laboratory values. For patients who reported SAMs, additional information around etiology and location were collected. Results: Of 3621 patients, 586 (394 BA; 192 placebo) reported intolerance to multiple statins because of SAMS or other AEs and received no statins during the studies. Mean baseline LDL-C was 148.7 mg/dL. After 12 weeks, BA significantly lowered LDL-C vs placebo (placebo-corrected, -26.5%; P < 0.001). Myalgia was the top reason for drug discontinuation, but was less common in the BA arm (17.7%) vs placebo (43.5%). CK > 5 х ULN was uncommon in both groups. Among AESIs (Table) , muscle disorders were reported by 12.7% (BA) vs 14.1% (placebo). Myalgia was less common with BA (4.6%) vs placebo (7.3%). Muscle spasms (4.1% vs 3.6%) and pain in extremity (3.3% vs 2.1%) were comparable between treatment groups. Muscular weakness was rare (0.5% BA, 1% placebo). Conclusion: Among the population of patients unable to use statins, BA significantly lowered LDL-C vs placebo without increasing muscle-related TEAEs. BA may be an appropriate lipid-lowering therapy for patients with hyperlipidemia who are statin intolerant.

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