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First-in-Man Safety...
First-in-Man Safety, Tolerability, and Pharmacokinetics of a Novel and Highly Selective Inhibitor of Matrix Metalloproteinase-12, FP-025 : Results from Two Randomized Studies in Healthy Subjects
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- Abd-Elaziz, Khalid (author)
- QPS-Netherlands
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- Voors-Pette, Christine (author)
- QPS-Netherlands
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- Wang, Kang Ling (author)
- Taipei Veterans General Hospital,National Yang-Ming University Taiwan
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- Pan, Sandy (author)
- Quest Pharmaceutical Services Co., Taiwan
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- Lee, Yisheng (author)
- Foresee Pharmaceuticals Co. Ltd
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- Mao, John (author)
- Foresee Pharmaceuticals Co. Ltd
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- Li, Yuhua (author)
- Foresee Pharmaceuticals Co. Ltd
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- Chien, Benjamin (author)
- Foresee Pharmaceuticals Co. Ltd
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- Lau, David (author)
- Foresee Pharmaceuticals Co. Ltd
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- Diamant, Zuzana (author)
- Lund University,Lunds universitet,Lungmedicin, allergologi och palliativ medicin,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Respiratory Medicine, Allergology, and Palliative Medicine,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine,University of Groningen,QPS-Netherlands,Catholic University of Leuven
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(creator_code:org_t)
- 2020-12-17
- 2021
- English.
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In: Clinical Drug Investigation. - : Springer Science and Business Media LLC. - 1173-2563 .- 1179-1918. ; 41:1, s. 65-76
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Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
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- ref (subject category)
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- By the author/editor
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Abd-Elaziz, Khal ...
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Voors-Pette, Chr ...
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Wang, Kang Ling
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Pan, Sandy
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Lee, Yisheng
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Mao, John
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show more...
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Li, Yuhua
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Chien, Benjamin
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Lau, David
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Diamant, Zuzana
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Pharmaceutical S ...
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Clinical Drug In ...
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Lund University