Novel Relaxin Receptor RXFP1 Agonist AZD3427 in the Treatment of Heart Failure: A Phase 1a/b, First-in-Human, Randomized, Single-Blind, Placebo-Controlled Study.

BACKGROUND: Heart failure mortality remains high despite recent progress in pharmacological treatment. AZD3427 is a selective long-acting analog of relaxin, a vasodilatory hormone with antifibrotic effects. We assessed the safety, pharmacokinetics, and pharmacodynamics of AZD3427 in healthy volunteers and patients with heart failure on standard-of-care therapy. METHODS AND RESULTS: In this first-in-human, phase 1a/b, randomized, single-blind, placebo-controlled study, healthy volunteers were randomized 6:2 to receive a single dose of AZD3427 or placebo by subcutaneous injection in 5 mixed-ethnicity cohorts (5, 10, 30, 90, or 270 mg) and 1 Japanese-descent cohort (270 mg), or by intravenous injection in 1 cohort (15 mg). After confirming safety and tolerability in healthy volunteers, 3 cohorts of patients with heart failure and left ventricular ejection fraction ≤40% and 3 cohorts with ejection fraction ≥41% were randomized 6:2 to receive 5 weekly doses of AZD3427 (5, 15, or 45 mg) or placebo by subcutaneous injection. In total, 56 healthy volunteers and 48 patients with heart failure were randomized. AZD3427 was well tolerated at all doses. After subcutaneous administration, AZD3427 was absorbed slowly, and exposure was approximately linear across the dose range. In patients with heart failure, AZD3427 terminal half-life was 13 to 14 days and there were numerical increases in stroke volume and estimated glomerular filtration rate. No treatment-emergent antidrug antibodies were detected. CONCLUSIONS: AZD3427 had favorable safety and pharmacokinetic profiles. Hemodynamic changes in patients with heart failure were consistent with the anticipated effects of a relaxin analog. These findings support further development of AZD3427 as a novel long-term treatment for patients with heart failure. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT04630067.

Cervical Cancer Prevention in Malaysia: Knowledge and Attitude of Undergraduate Pharmacy Students Towards Human Papillomavirus Infection, Screening and Vaccination in Malaysia.

This study was conducted to evaluate knowledge of undergraduate pharmacy students about human papillomavirus infection and their attitude towards its prevention. A cross-sectional survey was conducted in 270 undergraduate pharmacy students using a validated questionnaire to assess knowledge about human papillomavirus infection and cervical cancer and their attitudes towards human papillomavirus vaccines. Eighty-one percent of the respondents knew that human papillomavirus is a cause of cervical cancer, and 87.8 % knew that this infection is preventable. The gender of the respondents showed the strongest correlations with human papillomavirus knowledge. There were no significant correlations between the ethnic group of the respondents and their human papillomavirus-related knowledge. Higher perceptions of risk were associated with relationship status, and respondents who were in a relationship showed greater interest in vaccinating themselves; relationship status emerged as a unique predictor. The results indicated a moderately high level of knowledge and positive attitude towards human papillomavirus vaccination with few disagreements. The results of this study will help to develop and plan appropriate education campaigns for pharmacy students that aim to reduce human papillomavirus infection and, consequently, the incidence of and mortality caused by cervical cancer in Malaysia.