A phase 1 trial to assess P-gp mediated drug interactions with ASTX660 in healthy volunteers

Completed

• Conditions: acute myeloid leukemia; advanced solid tumors; lymphoma; 10024324

• Registration Number: NL-OMON50115
• Lead Sponsor: Astex Pharmaceuticals, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 2023-01-24
• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 48

Inclusion Criteria

1. Sex assigned at birth : male or female; females of nonchildbearing
potential, or postmenopausal.
2. Age : 18 to 65 years, inclusive, at screening.
3. Body mass index (BMI) : 18.0 to 32.0 kg/m2, inclusive, at screening.
4. Weight : >=50 kg.
5. Status : healthy subjects.

Exclusion Criteria

1. Employee of PRA or the Sponsor.
2. History of relevant drug and/or food allergies.
3. History of alcohol abuse or drug addiction (including soft drugs like
cannabis products) within 2 years prior to screening in the current study.
4. History or presence of atrioventricular block (any degree) or sick sinus
syndrome.
5. Subjects with increased cardiac risk evaluation based on the following
criteria:
• Smoking (no more than 2 packs of cigarettes) in the last 6 months prior to
admission, including use of nicotine-containing products (eg, snuff, nicotine
patch, nicotine chewing gum, mock cigarettes, e-cigarettes, or inhalers), or
positive cotinine test at screening (ie, cotinine value >500 ng/mL will be
excluded).
• Subjects with first-degree family history of ischemic cardiac event at a
young age (male <55; female <65 years).
• Subjects with family history of arrhythmia, sudden unexplained death at a
young age (before 40 years) in a first-degree relative, or long QT syndrome,
Torsades de Pointes (TdP), or a personal history of repeated or frequent
syncope or vasovagal episodes, or treatment for high blood pressure.
• History or presence of resuscitated arrest possibily due to TdP;
hypertension, angina, or severe peripheral arterial circulatory disorders.
• History or presence of risk factors for TdP (eg, congenital deafness, heart
failure, cardiomyopathy).
• History or presence of myocardial infarction, pulmonary congestion, cardiac
arrhythmia, or prolonged QT interval, or conduction abnormalities.
• History or presence of concomitant medications-induced QTc prolongation
within 30 days prior to screening.
• History or presence of hypokalemia, hypomagnesemia, or hypocalcemia.

See the protocol for the complete overview

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>- To determine the effect of P-glycoprotein (P-gp) inhibition by quinidine on<br /><br>pharmacokinetics (PK) of ASTX660<br /><br>- To determine the effect of P-gp inhibition by ASTX660 on PK of fexofenadine</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>- To determine the safety and tolerability of ASTX660 following oral<br /><br>administration alone or in combination with quinidine, a P-gp probe inhibitor;<br /><br>or with fexofenadine, a P-gp probe substrate</p><br>