Abstract:
BACKGROUND AND OBJECTIVES:Matrix metalloproteinases (MMPs) are proteases with different biological and pathological activities, and many have been linked to several diseases. Targeting individual MMPs may offer a safer therapeutic potential for several diseases. We assessed the safety, tolerability, and pharmacokinetics of FP-025, a novel, highly selective oral matrix metalloproteinase-12 inhibitor, in healthy subjects. METHODS:Two randomized, double-blind, placebo-controlled studies were conducted. Study I was a first-in-man study, evaluating eight single ascending doses (SADs) (50-800 mg) in two formulations: i.e., neat FP-025 in capsule (API-in-Capsule) and in an amorphous solid dispersion (ASD-in-Capsule) formulation. In Study II, three multiple ascending doses (MADs) (100, 200, and 400 mg, twice daily) of FP-025 (ASD-in-Capsule) were administered for 8 days, including a food-effect evaluation. RESULTS:Ninety-six subjects were dosed. Both formulations were well tolerated with one adverse event (AE) reported in the 800 mg API-in-Capsule SAD group and seven AEs throughout the MAD groups. The exposure to FP-025 was low with the API-in-Capsule formulation; it increased dose-dependently with the ASD-in-Capsule formulation, with which exposure to FP-025 increased in a greater-than-dose-proportional manner at lower doses (≤ 100 mg) but less proportionally at higher doses. The elimination half-life (t1/2) was between 6 (Study I) and 8 h (Study II). Accumulation of FP-025 was approximately 1.7-fold in the MAD study. Food intake delayed the rate of absorption, but without effect in the extent of absorption or bioavailability. CONCLUSION:FP-025 was well tolerated and showed a favorable pharmacokinetic profile following ASD-in-Capsule dosing. Efficacy studies in target patient populations, including asthma, chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis, are warranted. TRIAL REGISTRATION NUMBER:www.clinicaltrials.gov : NCT02238834 (Study I); NCT03304964 (Study II). Trial registration date: Study I was registered on 12 September 2014 while study II was registered on 9 October 2017.
journal_name
Clin Drug Investigjournal_title
Clinical drug investigationauthors
Abd-Elaziz K,Voors-Pette C,Wang KL,Pan S,Lee Y,Mao J,Li Y,Chien B,Lau D,Diamant Zdoi
10.1007/s40261-020-00981-9subject
Has Abstractpub_date
2021-01-01 00:00:00pages
65-76issue
1eissn
1173-2563issn
1179-1918pii
10.1007/s40261-020-00981-9journal_volume
41pub_type
杂志文章abstract:OBJECTIVE:To evaluate the effectiveness and safety of amlodipine in two cohorts of hypertensive patients, one newly diagnosed and the other previously diagnosed but not controlled with drug therapy, and to assess the risk factors for the entire sample at the outset of the study. PATIENTS AND DESIGN:We designed a postm...
journal_title:Clinical drug investigation
pub_type: 杂志文章
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journal_title:Clinical drug investigation
pub_type: 杂志文章,随机对照试验
doi:10.1007/s40261-015-0325-3
更新日期:2015-11-01 00:00:00
abstract::Intramuscular 17 α-hydroxyprogesterone caproate (Makena(®)), a synthetic progestin, is indicated to reduce the risk of preterm birth in women with a singleton pregnancy who have a history of a singleton spontaneous preterm birth. Makena(®) reduces the risk of preterm birth in this patient population, and is associated...
journal_title:Clinical drug investigation
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journal_title:Clinical drug investigation
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journal_title:Clinical drug investigation
pub_type: 杂志文章,多中心研究,随机对照试验
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journal_title:Clinical drug investigation
pub_type: 杂志文章,多中心研究,随机对照试验
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更新日期:2010-01-01 00:00:00
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journal_title:Clinical drug investigation
pub_type: 杂志文章,随机对照试验
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更新日期:2013-12-01 00:00:00
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journal_title:Clinical drug investigation
pub_type: 杂志文章
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更新日期:2017-01-01 00:00:00
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journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.2165/00044011-200424060-00003
更新日期:2004-01-01 00:00:00
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journal_title:Clinical drug investigation
pub_type: 杂志文章,随机对照试验
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更新日期:2016-11-01 00:00:00
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更新日期:2004-01-01 00:00:00
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abstract::We report the case of a 50-year-old male patient with idiopathic generalised epilepsy and porphyria cutanea tarda. Valproic acid and phenobarbital monotherapy controlled seizures but exacerbated porphyric symptomatology, while clobazam, clonazepam and lamotrigine monotherapy were well tolerated as regards porphyric di...
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更新日期:2018-01-01 00:00:00
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更新日期:2006-01-01 00:00:00
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更新日期:2016-04-01 00:00:00
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更新日期:2018-11-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Phenylephrine HCl 10 mg has been used as a nasal decongestant for over 50 years, yet only limited pharmacokinetic and metabolic data are available. The purpose of this study was to evaluate single-dose pharmacokinetics and safety of phenylephrine HCl 10, 20, and 30 mg and to assess cardiovascu...
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doi:10.1007/s40261-015-0311-9
更新日期:2015-09-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Concerns that antiepileptic brand-to-generic interchange results in disruption of seizure control are widespread. The objective of this study was to evaluate the safety and tolerability of the brand-to-generic levetiracetam switch in patients with focal or generalized epilepsy. METHODS:A prosp...
journal_title:Clinical drug investigation
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更新日期:2016-01-01 00:00:00
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journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.2165/00044011-200323010-00003
更新日期:2003-01-01 00:00:00
abstract:BACKGROUND:To evaluate the efficacy and safety of bronchoalveolar lavage (BAL) with diluted porcine surfactant in mechanically ventilated term infants with severe acute respiratory distress syndrome (ARDS) due to meconium aspiration syndrome (MAS). METHODS:Eight consecutive mechanically ventilated term infants with se...
journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.2165/00044011-200626010-00002
更新日期:2006-01-01 00:00:00
abstract:OBJECTIVES:This study investigated the pharmacokinetics and pharmacodynamics of a fixed-dose combination (FDC) tablet of olmesartan medoxomil 20 mg and amlodipine 5 mg (CS-8663) in healthy Chinese subjects. METHODS:This single-centre, open-label study was conducted in five healthy males and five females aged 18-45 yea...
journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.1007/s40261-012-0026-0
更新日期:2012-12-01 00:00:00
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更新日期:2004-01-01 00:00:00
abstract:OBJECTIVE:To compare the bioavailability of two 15mg ambroxol lozenges with a commercial 30mg ambroxol tablet. DESIGN:Open-label, two-way crossover study. METHOD:Each formulation was randomly administered to 20 healthy Thai volunteers (ten male and ten female) with a 1-week washout period between formulations. After ...
journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.2165/00044011-200323040-00007
更新日期:2003-01-01 00:00:00