didanosine (didanosine EC / Videx EC)

High potency and water dispersible Boswellia extract reduces pain and inflammation in subjects with osteoarthritis of the knee: A randomized, double-blind, placebo-controlled trial.

Nirvanashetty Somashekara S, Panda Sanjib Kumar SK

Boswellia serrata, also known as Indian frankincense, is a medicinal plant that has been used since ancient times in the traditional Indian medicine system, Ayurveda. Historically, Boswellia extract has been used to treat pain associated with osteoarthritis, rheumatoid arthritis, and tendonitis. In this randomized, double-blind, placebo-controlled study, 60 subjects aged 40 to 75 years, with mild to moderate knee osteoarthritis received either 100 mg once daily of standardized natural Boswellia extract (OLNP-27) or placebo for 8-weeks. The subjects were monitored for outcome measures such as total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, WOMAC subscales (pain, stiffness, and physical function) score and visual analogue score on day 7, 15, 30, and 60 post supplementation. OLNP-27 significantly (P < .05) reduced the total WOMAC score, pain score, stiffness score, visual analogue score score and improved the physical function than the placebo. OLNP-27 also decreased the inflammatory marker high-sensitivity-CRP significantly compared to placebo group. The statistically significant reduction in pain and stiffness was observed as quickly as 7 days of supplementation with OLNP-27 indicating the quick onset of action. It also was found to be safe and well tolerated during this study. Based on the current study findings, it can be concluded that OLNP-27 is an effective and safe natural option for the management of symptoms associated with osteoarthritis of the knee.

A PBPK-VBE approach for bioequivalence extrapolation of senaparib capsule strengths in the context of nonlinear pharmacokinetics: bridging from the clinical starting dose to the linear pharmacokinetic range.

Wu Xiaofei X, Wang Ziyang Z, He Yanna Y, Wu Keheng K et al.

Senaparib (Sepalna®), a novel oral poly (adenosine diphosphate -ribose) polymerase (PARP) 1/2 inhibitor, was approved in China in 2025 as maintenance therapy for advanced ovarian cancer. The recommended starting dose is 100 mg once daily, which may be adjusted to 80 mg, 60 mg, or 40 mg to manage adverse events. While conventional bioequivalence (BE) clinical studies established equivalence between the 10 mg and 20 mg capsules strengths at the 100 mg dose level, these findings cannot be extrapolated to the lower dose range due to senaparib's nonlinear pharmacokinetics and the current absence of definitive regulatory guidance for such scenarios. This study aimed to evaluate the bioequivalence between the 10 mg and 20 mg capsule strengths of senaparib, a drug exhibiting nonlinear pharmacokinetics, across the 20-80 mg dose range. We developed and validated an integrated approach combining physiologically based pharmacokinetic (PBPK) modeling with in vitro dissolution data to evaluate virtual bioequivalence (VBE) between the two capsule strengths across the 20-80 mg dose range. Under all evaluated conditions including variations in sample size, intra-individual variability levels, and prandial states (fasted and fed), the geometric mean ratios (GMRs) of key pharmacokinetic (PK) parameters consistently approached 100%, thereby confirming bioequivalence across the specified dosing range. This PBPK-VBE framework provides supportive evidence for bioequivalence bridging of senaparib capsule strengths across the linear dose range, illustrating the potential utility of this approach for formulation bridging when direct clinical BE studies across all dose levels are impractical.

Efficacy and Safety of Tofacitinib Versus Placebo in Patients With Early-Grade Knee Osteoarthritis: A Randomized, Double-Blind, Placebo-Controlled Trial.

Fasni Rini R, Tripathy Sujit Kumar SK, Mishra Archana A, Khan Shahnawaz S et al.

Knee osteoarthritis causes major pain and disability, yet disease-modifying drugs remain limited. Tofacitinib, an oral Janus kinase (JAK) inhibitor, suppresses pro-inflammatory cytokine signaling implicated in osteoarthritis but is unexplored in the knee; we evaluated it versus placebo in early-grade disease. In this single-center, randomized, double-blind, placebo-controlled trial, 100 patients with Kellgren-Lawrence Grades 1 and 2 knee osteoarthritis were randomized to tofacitinib 11 mg extended-release once daily (n = 49) or placebo (n = 51) for 12 weeks. The primary outcome was change in VAS pain to Week 12; secondary outcomes were WOMAC, Oxford Knee Score, EQ-5D-5L, and analgesic use, assessed to Week 12 and a Month-6 follow-up, and analyzed by intention-to-treat with a mixed model for repeated measures. Baseline characteristics were balanced. Both groups improved within-group during treatment (p < 0.001), but between-group differences were not significant; the Week-12 VAS effect (tofacitinib minus placebo) was +0.02 (95% CI -0.84 to 0.89), with WOMAC, Oxford Knee Score, and EQ-5D-5L likewise excluding their minimal clinically important differences. Improvements rebounded toward baseline by Month 6. Drug-related adverse events were more frequent with tofacitinib (14.3% vs. 0%, p = 0.005) but were gastrointestinal and self-limiting. Tofacitinib was not superior to placebo in early-grade knee osteoarthritis, and the large within-group improvement rebounded toward baseline by 6 months, consistent with a predominantly non-specific (contextual) response. Because participants were selected radiographically without inflammatory phenotyping, these findings do not support tofacitinib in unselected early-grade disease but cannot exclude benefit in an inflammatory phenotype; future trials should stratify accordingly, with longer follow-up and structural outcomes. Clinical Trials Registry of India: CTRI/2025/07/090567.

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