Two-Year Analysis of a New Oral Testosterone Undecanoate (TU) Formulation in Hypogonadal Men: Efficacy, Impact on Psychosexual Function, and Safety.

BACKGROUND: Long-term data evaluating the efficacy and safety of oral testosterone undecanoate (oral TU; JATENZO) in adult hypogonadal men provides important information for healthcare professionals who prescribe testosterone replacement therapy (TRT). AIM: To determine the efficacy and safety of long-term oral TU therapy, including its impact on total testosterone (T) levels and psychosexual functioning. METHODS: Hypogonadal men, between 18 and 75 years old, (mean age 56.2; 87.2% white) who completed a 12-month, open-label, multicenter, randomized, active-controlled trial were given the opportunity to enroll in a 12-month extension study. Among the 129 eligible TU-treated subjects, 86 chose this option, and 69 completed 24 months of uninterrupted oral TU therapy. OUTCOMES: The efficacy of oral TU was documented by measuring total serum T concentrations; sexual function was measured using the Psychosexual Daily Questionnaire (PDQ). For safety, liver function tests, cardiovascular endpoints, and prostate health were measured. RESULTS: Over 2 years, total serum T concentrations for patients treated with oral TU were in the eugonadal range (300-1,000 ng/dL [10-35 nmol/L]; mean ± SD: 617 ± 427 ng/dL [21 ± 15 nmol/L]) and increased significantly from baseline (P < .0001). For sexual function, mean score changes versus baseline for all PDQ domains at all time points were significantly improved (P < .0011 for all). For the sexual activity and sexual desire components, patient scores were consistently greater than validated thresholds for clinically meaningful change. Typical T-induced safety changes were observed, including a 3-6 mm Hg increase in systolic blood pressure (P < .05); a slight increase in hematocrit (P < .0001) that stayed <48% throughout the study; no clinically significant changes in prostate-specific antigen levels; and decreased high-density lipoprotein cholesterol (-9.8 ± 0.9 mg/dL from baseline; P < .0001). There were no clinically significant changes from baseline in liver function tests. CLINICAL IMPLICATIONS: Over 2 years of treatment, this novel oral TU formulation maintained total T concentrations in mideugonadal ranges, with improvements in sexual function and no clinically significant changes in liver function or other safety concerns previously associated with oral TRT. STRENGTHS & LIMITATIONS: These are the first long-term data to evaluate the efficacy and safety of a novel formulation of oral TU; the comparative long-term safety of oral TU would be strengthened by confirmatory studies versus other TRT formulations. CONCLUSION: Oral TU offers a safe and effective long-term treatment option for men with hypogonadism. Honig S, Gittelman M, Kaminetsky J, et al. Two-Year Analysis of a New Oral Testosterone Undecanoate (TU) Formulation in Hypogonadal Men: Efficacy, Impact on Psychosexual Function, and Safety. J Sex Med 2022;19:1750-1758.

Cethromycin versus clarithromycin for community-acquired pneumonia: comparative efficacy and safety outcomes from two double-blinded, randomized, parallel-group, multicenter, multinational noninferiority studies.

Community-acquired pneumonia (CAP) continues to be a major health challenge in the United States and globally. Factors such as overprescribing of antibiotics and noncompliance with dosing regimens have added to the growing antibacterial resistance problem. In addition, several agents available for the treatment of CAP have been associated with serious side effects. Cethromycin is a new ketolide antibiotic that may provide prescribing physicians with an additional agent to supplement a continually limited armamentarium. Two global phase III noninferiority studies (CL05-001 and CL06-001) to evaluate cethromycin safety and efficacy were designed and conducted in patients with mild to moderate CAP. Study CL05-001 demonstrated an 83.1% clinical cure rate in the cethromycin group compared with 81.1% in the clarithromycin group (95% confidence interval [CI], -4.8%, +8.9%) in the intent to treat (ITT) population and a 94.0% cethromycin clinical cure rate compared with a 93.8% clarithromycin cure rate (95% CI, -4.5%, +5.1%) in the per protocol clinical (PPc) population. Study CL06-001 achieved an 82.9% cethromycin clinical cure rate in the ITT population compared with an 88.5% clarithromycin cure rate (95% CI, -11.9%, +0.6%), whereas the clinical cure rate in the PPc population was 91.5% in cethromycin group compared with 95.9% in clarithromycin group (95% CI, -9.1%, +0.3%). Both studies met the primary endpoints for clinical cure rate based on predefined, sliding-scale noninferiority design. Therefore, in comparison with clarithromycin, these two noninferiority studies demonstrated the efficacy and safety of cethromycin, with encouraging findings of efficacy in subjects with Streptococcus pneumoniae bacteremia. No clinically significant adverse events were observed during the studies. Cethromycin may be a potential oral therapy for the outpatient treatment of CAP.

The CTLA4 -819 C/T and +49 A/G dimorphisms are associated with Type 1 diabetes in Egyptian children.

BACKGROUND: Type 1 diabetes (T1D) is an organ-specific autoimmune disease characterized by T cell-mediated destruction of pancreatic islets. T cell proliferation is negatively regulated by cytotoxic lymphocyte antigen-4 (CTLA-4). CTLA-4 polymorphisms are associated with T1D in some but not all populations. AIMS: The study was conducted to investigate the association of the C-819T and A+49G single nucleotide polymorphisms (SNP) of CTLA-4 gene in T1D patients in the Egyptian population. METHODS: The association of the C-819T SNP in intron 1 and A+49G SNP in exon 1 of the CTLA-4 gene with T1D were investigated in 396 Egyptian patients 24 years old, with the same ratio of males to females in both groups. The diagnosis of T1D was made on the basis of ketoacidosis or ketosis with severe symptoms of acute onset at presentation and continuous dependence on insulin. Controls were negative for anti-GAD antibodies and were greater than 24 years of age. Genotyping was performed using single strand conformation polymorphism (SSCP), temperature gradient gel electrophoresis (TGGE), and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: The results demonstrated an association of the C-819T and A+49G SNPs in the CTLA-4 gene with T1D patients (P=0.0047) and (P=0.000575), respectively. Moreover, this association was stratified by gender and age to female patients with age at onset 0-5 years old (P=0.0186) and (P=0.00115) more than male patient with the age at onset 0-5 years old (P= 0.3120) and (P=0.345161), respectively. CONCLUSION: The results support an association of the C-819T and A+49G SNPs in the CTLA-4 gene with Egyptian children, specifically, females of onset age 0-5 years old.

Hydrocortisone butyrate 0.1% cream in the treatment of chronic dermatitis.

This multicenter, randomized, double-blind clinical trial involving 89 subjects (86 with chronic hand dermatitis and 3 with atopic dermatitis) compared the safety, efficacy, and cosmetic acceptability of 4 medium-potency topical corticosteroid products: hydrocortisone butyrate (HB) 0.1% cream (Locoid Lipocream), fluticasone propionate (FP) 0.05% cream (Cutivate), prednicarbate (PC) 0.1% cream (Dermatop), and mometasone furoate (MF) 0.1% cream (Elocon). Subjects were randomly assigned to 1 of 3 treatment groups (HB vs FP, HB vs PC, or HB vs MF) and further randomized to HB on the right or the left side, and FP, PC, or MF on the contralateral side. Treatments were self-administered twice daily for 2 weeks. Assessments of efficacy were based on the investigator ratings of signs and the subject ratings of signs and symptoms. Cosmetic acceptability was assessed by direct comparisons between products using a subject questionnaire. The results indicated comparable efficacy of all 4 medium-potency corticosteroid products and suggested that, compared to other corticosteroid creams, the HB vehicle yielded somewhat greater subject preference with respect to cosmetic appeal.