[Translation] A randomized, double-blind, multicenter Phase II clinical study to evaluate the efficacy and safety of two different dose groups of AK3280 compared with the placebo control group in patients with idiopathic pulmonary fibrosis

通过用力肺活量占正常预计值的百分比（%FVC），评价AK3280在IPF患者中相对于安慰剂对照组的疗效为主要研究目的。

[Translation]

The main study objective was to evaluate the efficacy of AK3280 in IPF patients compared with the placebo control group by measuring the percentage of forced vital capacity (%FVC).

Start Date21 Jul 2022

Sponsor / Collaborator

Shanghai Ark Biopharmaceutical Co., Ltd.Startup

CTR20220666 / CompletedPhase 1/2

一项随机、双盲、安慰剂自身对照以评价 AK3280乳膏在中国增生性瘢痕切除患者中的安全耐受性及疗效的 I/II 期临床研究

[Translation] A randomized, double-blind, placebo-controlled phase I/II clinical study to evaluate the safety, tolerability and efficacy of AK3280 cream in Chinese patients undergoing hypertrophic scar excision

本研究主要目的为评估 AK3280 乳膏在增生性瘢痕切除患者中的安全性和耐受性，次要目的为评价 AK3280乳膏不同剂量局部皮肤用药对预防增生性瘢痕术后复发的疗效和监测 AK3280 乳膏皮肤用药在增生性瘢痕切除患者血浆中的药物浓度。

[Translation]

The primary purpose of this study was to evaluate the safety and tolerability of AK3280 cream in patients undergoing hypertrophic scar excision. The secondary purpose was to evaluate the efficacy of different doses of AK3280 cream for topical skin application in preventing postoperative recurrence of hypertrophic scars and to monitor the drug concentration of AK3280 cream for topical skin application in the plasma of patients undergoing hypertrophic scar excision.

Start Date08 Jul 2022

Sponsor / Collaborator

Shanghai Ark Biopharmaceutical Co., Ltd.Startup

NCT05424887 / Not yet recruitingPhase 2

A Randomized, Double-blind, Multi-center Phase II Clinical Study to Evaluate the Efficacy and Safety of Two Different Dose Groups of AK3280 in Patients With Idiopathic Pulmonary Fibrosis (IPF) Compared to the Placebo Control Group

This study is a randomized, double-blind, placebo-controlled, multi-center phase II clinical study conducted in China to compare the efficacy and safety of two different dose groups of AK3280 in IPF patients compared to the placebo control group.

Start Date01 Jul 2022

Sponsor / Collaborator

Shanghai Ark Biopharmaceutical Co., Ltd.Startup

[+1]

100 Clinical Results associated with GDC-3280

100 Translational Medicine associated with GDC-3280

100 Patents (Medical) associated with GDC-3280

Literatures (Medical) associated with GDC-3280

06 Nov 2023·Molecular Pharmaceutics

Comparative Evaluation of Particle Size Reduction, Salt Formation, and Amorphous Formulation on the Biopharmaceutical Performance of a Weak Base Drug Candidate

Article

Author: Zhang, Wei ; Ma, Fang ; Hou, Hao Helen ; Weitz, Benjamin W ; Nagapudi, Karthik ; Chiang, Po-Chang ; Jia, Wei ; Chen, Yuan

Various approaches have been developed to enhance the solubility or dissolution rate for the delivery of poorly water-soluble molecules. In this work, guided by an in silico solubility sensitivity analysis for oral absorption, a comparative assessment of the biopharmaceutical performance of a jet-milled free base, a tosylate salt, and a 50:50 (w/w) amorphous solid dispersion (ASD) with hydroxypropyl methylcellulose acetate succinate (HPMCAS) of a weak base drug candidate, GDC-3280, was conducted. Successful particle size reduction without amorphization or form change was confirmed for the jet-milled free base. The potential of solubility enhancement and desupersaturation risk were identified for tosylate salt and ASD formulation by measurements of tosylate salt solubility product constant (K_sp) and amorphous solubility of GDC-3280. In vitro dissolution testing demonstrated dissolution rate improvement for the jet-milled free base when compared with the unmilled free base and confirmed solubility enhancement followed by desupersaturation for GDC-3280 tosylate salt and ASD formulation. A crystallization inhibitor, hydroxypropyl methylcellulose (HPMC), was found to slow down the desupersaturation of tosylate salt solution, providing general insights for the development of pharmaceutical salts with disproportionation risks. Finally, a pharmacokinetic study in dogs showed that the in vivo exposure increased by 1.7- to 2-fold for the tosylate salt and ASD formulation compared with the jet-milled free base, consistent with the in silico solubility sensitivity analysis for the fraction of drug absorbed. Overall, this work provides insights into the evaluation of multiple formulation approaches for enhancing the biopharmaceutical performance of poorly water-soluble drugs.

01 Aug 2021·Pulmonary Pharmacology & TherapeuticsQ3 · MEDICINE

A phase 1, randomized study to evaluate safety, tolerability, and pharmacokinetics of GDC-3280, a potential novel anti-fibrotic small molecule, in healthy subjects

Q3 · MEDICINE

Article

Author: Cabanski, Christopher R ; Fong, Alice ; Harris, Jeffrey M ; Chen, Yuan ; Pan, Lin ; Bush, Jim ; Wang, Jianshuang ; Cheung, Dorothy ; Ding, Han Ting

BACKGROUNDIdiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease. Although anti-fibrotic treatments, such as pirfenidone, are available that reduce the rate of disease progression, these medications have limitations in tolerability, and IPF patients still have poor prognoses. GDC-3280, an orally available small molecule that was designed to improve upon pirfenidone's activity, has anti-fibrotic activity in animal models. This first-in-human, phase 1 trial evaluated GDC-3280 to determine its safety, tolerability, and pharmacokinetics (PK).METHODSSingle and multiple ascending-doses of GDC-3280 were administered to healthy volunteers in two parts. Part A consisted of 6 treatment groups, each receiving a single, oral dose of GDC-3280 (25-1600 mg) or placebo in the fasted state. Part A also assessed the effect of food and coadministration of a proton pump inhibitor (rabeprazole) on the tolerability and PK of single doses of 400- and 800-mg GDC-3280. Part B consisted of 3 treatment groups who received either 200- or 275-mg GDC-3280 twice daily or 525-mg once daily after a low-fat meal for 7 days. The trial monitored treatment-emergent adverse events (TEAEs) and assessed the pharmacokinetics of GDC-3280 in blood and urine samples.RESULTSFifty-six subjects (42 GDC-3280, 14 placebo) in Part A and 24 subjects (18 GDC-3280, 6 placebo) in Part B received treatment. No deaths, serious adverse events, or dose-limiting adverse events occurred, and no subjects withdrew due to a TEAE. In both Parts A and B, most TEAEs were mild. The most frequent TEAEs in Part A were headache and nausea. TEAEs occurred more often when GDC-3280 was administered with food. Pretreatment and coadministration with rabeprazole had no effect on GDC-3280 tolerability. In Part B, the most frequent TEAEs were nausea, dizziness, nasal congestion, and cough. Transient, treatment-related increases in serum creatinine occurred at doses greater than 400 mg in Part A (12%-18% from baseline) and after multiple doses in each group in Part B (20%-34% from baseline). GDC-3280 was generally readily absorbed with a median t_max < 4.0 h following single- or repeat-dose oral administration. In Part A, less-than-dose-proportional increases in systemic exposure occurred, and in Part B, dose-proportional increases occurred within the dose range tested. At doses of 200 mg or lower, more than 50%-70% of orally administered doses were recovered in urine as unchanged GDC-3280 when subjects received a single dose of GDC-3280, suggesting renal excretion is one of the major routes of elimination. Administration of single doses of 400- and 800-mg GDC-3280 after a meal caused statistically significant increases in exposure due to increased rates of absorption compared to the fasted state. Pretreatment and coadministration of rabeprazole dosing led to decreases in exposure compared to GDC-3280 alone, indicating a weak drug-drug interaction. Following repeat dose administration, steady-state plasma concentrations of GDC-3280 were achieved within 2 days with an apparent terminal half-life (t_1/2) between 5 and 6 h.CONCLUSIONSSingle and multiple doses of GDC-3280 were generally well tolerated, with acceptable safety and pharmacokinetic profiles that support twice-daily, oral administration with food in future clinical trials.

01 Apr 2019·Biomedical ChromatographyQ4 · MEDICINE

Determination of a novel antifibrotic small molecule GDC‐3280 in human plasma and urine by liquid chromatography tandem mass spectrometry to support its first‐in‐human clinical trial

Q4 · MEDICINE

Article

Author: McKnight, Janine ; Ding, Xiao ; Pan, Lin ; Dean, Brian ; Wang, Jianshuang ; Van Parys, Michael ; Cheung, Dorothy ; Chen, Yuan ; Milanowski, Dennis

AbstractA specific and robust LC–MS/MS method was developed and validated for the quantitative determination of GDC‐3280 in human plasma and urine. The nonspecific binding associated with urine samples was overcome by the addition of CHAPS. The sample volume was 25 μL for either matrix, and supported liquid extraction was employed for analyte extraction. d6‐GDC‐3280 was used as the internal standard. Linear standard curves (R2 > 0.9956) were established from 5.00 to 5000 ng/mL in both matrices with quantitation extended to 50,000 ng/mL through dilution. In plasma matrix, the precision (RSD) ranged from 1.5 to 9.9% (intra‐run) and from 2.4 to 7.2% (inter‐run); the accuracy (RE) ranged from 96.1 to 107% (intra‐run) and from 96.7 to 104% (inter‐run). Similarly, in urine the precision was 1.5–6.2% (intra‐run) and 1.9–6.1% (inter‐run); the accuracy was 83.1–99.3% (intra‐run) and 87.1–98.3% (inter‐run). Good recovery (>94%) and negligible matrix effect were achieved in both matrices. Long‐term matrix stability was established for at least 703 days in plasma and 477 days in urine. Bench‐top stability of 25 h and five freeze–thaw cycles were also confirmed in both matrices. The method was successfully implemented in GDC‐3280's first‐in‐human trial for assessing its pharmacokinetic profiles.

100 Deals associated with GDC-3280

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Cicatrix	Phase 2	CN	Shanghai Ark Biopharmaceutical Co., Ltd.Startup	08 Jul 2022
Cicatrix, Hypertrophic	Phase 2	CN	Shanghai Ark Biopharmaceutical Co., Ltd.Startup	01 Jul 2022
Idiopathic Pulmonary Fibrosis	Phase 2	CN	Shanghai Ark Biopharmaceutical Co., Ltd.Startup	01 Jul 2022

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