Safety, pharmacokinetics and pharmacodynamics of a novel anti-asthmatic drug, XC8, in healthy probands
Copyright © 2019 Elsevier Ltd. All rights reserved..
INTRODUCTION: XC8 (histamine glutarimide) is a novel agent which targets eosinophilic migration and mast cell degranulation and has shown anti-asthmatic effects in animal studies.
OBJECTIVE: The objective of this placebo-controlled phase 1 study was to assess the safety of oral XC8 and to evaluate its pharmacokinetic and pharmacodynamic properties.
METHODS: 32 healthy volunteers in three dose-escalation treatment groups (10 mg [n = 8], 50 mg [n = 8] and 200 mg [n = 16]) were randomized in a 3:1 ratio to XC8 or placebo respectively. The subjects received a single dose of the drug at Day 1 and then once-daily for 14 days (Days 8-21).
RESULTS: No severe adverse events occurred. The number of adverse events was similar in the treatment arms compared to placebo and all subjects completed the study as planned. No clinically significant changes occurred in hematologic and biochemical blood tests in subjects receiving XC8. The pharmacokinetic data showed similar dose and time dependent mean plasma XC8 concentrations after single (Day 1) and multiple (Day 21) dosing. The mean maximum concentrations were 114-1993 ng/mL after single and 115-2089 ng/mL after multiple dosing. The mean times to maximum concentration were 0.68-1.01 and 0.67-0.98 h, respectively. There was no evidence for accumulation of XC8 after multiple dosing.
CONCLUSION: XC8 was safe and well tolerated. A phase 2 study is being performed to further evaluate the potential role of XC8 in asthma treatment.
TRIAL REGISTRATION: ClinicalTrials.gov, NCT02882217.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:59 |
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| Enthalten in: |
Pulmonary pharmacology & therapeutics - 59(2019) vom: 10. Dez., Seite 101852 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Renner, Andreas [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 03.09.2020 Date Revised 09.11.2020 published: Print-Electronic ClinicalTrials.gov: NCT02882217 Citation Status MEDLINE |
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| doi: |
10.1016/j.pupt.2019.101852 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 500 | |a ClinicalTrials.gov: NCT02882217 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2019 Elsevier Ltd. All rights reserved. | ||
| 520 | |a INTRODUCTION: XC8 (histamine glutarimide) is a novel agent which targets eosinophilic migration and mast cell degranulation and has shown anti-asthmatic effects in animal studies | ||
| 520 | |a OBJECTIVE: The objective of this placebo-controlled phase 1 study was to assess the safety of oral XC8 and to evaluate its pharmacokinetic and pharmacodynamic properties | ||
| 520 | |a METHODS: 32 healthy volunteers in three dose-escalation treatment groups (10 mg [n = 8], 50 mg [n = 8] and 200 mg [n = 16]) were randomized in a 3:1 ratio to XC8 or placebo respectively. The subjects received a single dose of the drug at Day 1 and then once-daily for 14 days (Days 8-21) | ||
| 520 | |a RESULTS: No severe adverse events occurred. The number of adverse events was similar in the treatment arms compared to placebo and all subjects completed the study as planned. No clinically significant changes occurred in hematologic and biochemical blood tests in subjects receiving XC8. The pharmacokinetic data showed similar dose and time dependent mean plasma XC8 concentrations after single (Day 1) and multiple (Day 21) dosing. The mean maximum concentrations were 114-1993 ng/mL after single and 115-2089 ng/mL after multiple dosing. The mean times to maximum concentration were 0.68-1.01 and 0.67-0.98 h, respectively. There was no evidence for accumulation of XC8 after multiple dosing | ||
| 520 | |a CONCLUSION: XC8 was safe and well tolerated. A phase 2 study is being performed to further evaluate the potential role of XC8 in asthma treatment | ||
| 520 | |a TRIAL REGISTRATION: ClinicalTrials.gov, NCT02882217 | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a Randomized Controlled Trial | |
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