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AIM: To explore the reasons for screening failure of healthy subjects in clinical trials of orally inhaled drug products (OIDPs). METHODS: Screening data of 1 432 healthy subjects who participated in clinical trials of OIDPs were collected. The main reasons for the screening failure, gender differences in screening failure rate and the correlation between age and screening failure rate were summarized and analyzed. RESULTS: The screening failure rate was 72.4 % and increased with age. The failure rate was slightly higher in females than in males. Besides abnormal vital signs (17.3%), abnormal laboratory test results (16.5%) and withdrawal of consent (7.6%), poor venous condition (13.9%), positive for cigarette test results (12.6%) and failure in inhalation training (7.1%) were also the other three main reasons affecting the screening success rate. Abnormal vital signs and poor venous conditions were the primary screening failure reasons for males and females, respectively. CONCLUSION: The screening success rate could be improved by informing fully and communicating effectively, selecting young subjects with strong understanding abilities, and enhancing the training skills of investigators.
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AIM: To investigate the safety of bioequivalence (BE) studies of orally inhaled drug products (OIDPs) conducted by Phase I clinical Research Center of our hospital. METHODS: The safety data were collected from 482 healthy subjects enrolled in 20 OIDPs BE studies in Wuxi People's hospital from 2017 to 2022. The difference of adverse events (AEs) between test preparation and reference preparation were compared, as well as the influence of gender, age, mechanism of drug action and device type on AE were analyzed. RESULTS: A total of 102 cases of AEs were occurred in 77 subjects (16.0%, 77/482), 87 cases of AEs were related to experimental drugs, all AEs were mild or moderate, and no serious adverse events occurred. There was no difference in the incidence of AE between test preparation and reference preparation. In addition, gender, age, mechanism of drug action and device type had no significant effects on AEs. CONCLUSION: In 20 bioequivalence studies of OIDPs, OIDPs were safe and well tolerated in healthy subjects after dosing, and safety features of generic OIDPs and original drug were basically similar.
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Orally inhaled drug products (OIDPs) play a great role in the pharmacological treatment of chronic obstructive pulmonary disease (COPD) and asthma. There is an unmet clinical need for OIDPs. Pharmacodynamics-Bioequivalence studies (PD-BE) are recommended by several national guidelines as important research methods for bioequivalence study of OIDPs. It can effectively bridge the gap between in vitro studies and PK-BE studies in evaluating the efficacy and safety consistency of generic drugs with the original drugs. There are two research methods for PD-BE, using a diastolic model or an excitation model. The different methods use different metrics to evaluate efficacy. The more commonly used metrics include Forced Expiratory Volume in the First Second (FEV1), Specific Airway Conductance (sGaw), Peripheral Airway Resistance (R5-20), and stimulant concentration/dose (PC20/PD20). PD-BE studies using FEV1 as an efficacy metric is also recommended by the FDA (Food and Drug Administration), EMA (European Medicines Agency) and NMPA (National Medical Products Administration) guidelines and is widely accepted by investigators. In such PD-BE studies, the trial protocols for different OIDPs drugs are relatively consistent in terms of trial design, trial data processing, and equivalence evaluation criteria, while there are detailed differences in terms of target population, single/multiple dosing, dose administration, and collection site design. This paper reviews the progress of PD-BE studies in the bioequivalence evaluation of OIDPs by combining national guidelines and PD-BE-related studies of OIDPs published in the last five years, with a view to providing important theoretical information for PD-BE studies of OIDPs.
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Intralesional injection is a common method among various therapeutic choices for the treatment of Infantile Hemangiomas. This article reviews the clinical application of intralesional injections for infantile hemangiomas, discusses indications for intralesional injection treatment and evaluates the safety and efficacy of different injected drugs.
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Objective To investigate the expression of lung keratinocyte growth factor receptor (KGFR) in rats with acute spinal cord injury (ASCI) in different time points and its role in lung edema.Methods Thirty-two adult Wistar rats weighing 240 g to 260 g were assigned to experimental group (n =16) and control group (n =16) according to the random number table.Each group consisted of time points of 24 hours,3 days,1 week and 2 weeks after the modeling (4 rats per time point).A rat model of ASCI in experimental group was induced at C7 segment by dropping a weight of 10 g from the height of 2.5 cm (Allen' s method).In control group,laminas were removed only,leaving spinal cord at C7 intact.Rats were sacrificed at each time point for measurement of lung wet/dry weight ratio,Western blot analysis of expression of lung KGFR protein and RT-qPCR detection of lung KGFR mRNA expression.Results After ASCI in rats,the expressions of lung KGFR protein and mRNA began to drop at 24 hours (0.23 ±0.06,0,012 1 ±0.002 3),reached the trough at 3 days (0.17 ±0.04,0.008 5 ±0.001 7)and picked up at 1 week.Expression of lung KGFR mRNA in experiment group showed statistically significant difference from that in control group at 24 hours and 3 days (P ＜ 0.05),whereas in each time point the difference of KGFR protein expression between experiment and control groups was statistically significant(P ＜0.05).Variation trend of KGFR expression was in parallel with the severity degree of pulmonary edema.Conclusion Lung KGFR presents significant down-regulation in ASCI rats and this may be associated with the development of pulmonary edema after ASCI.
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ObjectiveTo investigate the effects of astragalin on pulmonary edema after acute cervical spinal cord injury in rats.MethodsA total of 200 adult Wistar rats weighing 240-250 g were randomly divided into five groups:astragalin group,low concentration astragalin group,physiological saline group,blank group and sham group,with 40 rats in each group.The rats with cervical spinal cord injury were induced at C7 by modified Allen' s method,with the dropping weight of 10 × 2.5 g · cm.In the sham group,the laminas were removed only,leaving spinal cord at the C7 intact.Each group was further divided into four time points:24 hours,3 days,1 week and 2 weeks after the modeling,with 10 rats in each time point,according to the specimen collection time.Rats were sacrificed at different time points to observe the pathological change of the lung tissue using optical microscope,measure the lung wet/dry weight ratio (W/D) and protein concentrations of the serum and bronchoalveolar lavage fluid and calculate the lung W/D and lung permeability index (LPI).ResultsAt the same instant,the W/D and LPI in the astragalin group and low concentration astragalin group were lower than those in physiological saline group and blank group,with the lowest value in the astragalin group at day 3 after injury ( P ＜0.05 ).ConclusionsRats with acute cervical spinal cord injury may cause pulmonary edema,which can be efficiently alleviated through early use of astragalin.