An open-label study to investigate the effects of emvododstat on the pharmacokinetics of CYP2D6 and BCRP substrates in healthy volunteers
- Conditions
- Cancer10024324Acute Leukemias
- Registration Number
- NL-OMON50753
- Lead Sponsor
- PTC Therapeutics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 36
1. Healthy adult, non-smokers (no use of tobacco products within 6 months prior
to Screening), >=18 and <=65 years of age.
2. Body mass index >18.0 and <30.0 kg/m2 and body weight >=50.0 kg and <=110.0 kg.
3. Ability to swallow tablets
4. Women of child-bearing potential (as defined in (CTFG 2014)) must have a
negative pregnancy test at Screening and agree to abstinence or the use at
least one of the following highly effective forms of contraception (with a
failure rate of <1% per year when used consistently and correctly) in addition
to barrier method for their sexual partner. Contraception or abstinence must be
continued for the duration of the study following discharge from the hospital,
and for up to 180 days after the last dose of study drug:
- Combined (estrogen and progestogen containing) hormonal contraception
associated with inhibition of ovulation:
- Oral
- Intravaginal
- Transdermal
- Progestogen-only hormonal contraception associated with inhibition of
ovulation:
- Oral
- Injectable
- Implantable
- Intrauterine device
- Intrauterine hormone-releasing system
- Vasectomized partner with confirmed azoospermia
All females will be considered of child-bearing potential unless they are
postmenopausal (at least 12 months consecutive amenorrhea in the appropriate
age group without other known or suspected cause) or have been sterilized
surgically (eg, bilateral tubal ligation, hysterectomy, bilateral oophorectomy).
5. Sexually active and fertile males must use a condom during intercourse while
taking study drug and for 90 days after stopping study drug and should not
father a child in this period. A condom is required to be use by vasectomized
men in order to prevent delivery of the drug via seminal fluid.
Further criteria apply
1. For Part 1 (CYP2D6 substrate), subjects who are poor metabolizers of CYP2D6
isoenzymes are excluded.
2. Pregnant or lactating subjects or those sexually active subjects who are
unwilling to comply with proper birth control methods; females of child-bearing
potential must have a negative pregnancy test at Screening and during the
Baseline Visit.
3. Aspartate aminotransferase or alanine aminotransferase above the upper limit
of normal (ULN) at the time of Screening or Baseline. Values above ULN may be
allowed if considered not clinically significant at the discretion of the
Investigator.
4. International normalized ratio >=1.5×ULN at time of Screening or Baseline or
clinically significant bleeding, as determined by the Investigator.
5. Serum creatinine >=1.5×ULN at time of Screening or Baseline.
Further criteria apply
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Endpoints for assessment of emvododstat as a perpetrator when administered with<br /><br>a CYP2D6 substrate (dextromethorphan) and BCRP substrate (rosuvastatin):<br /><br>PK Parameters:<br /><br>- Dextromethorphan and dextrophan: AUC0-t, AUC0-inf, Cmax<br /><br>- Rosuvastatin: AUC0-t, AUC0-inf, Cmax</p><br>
- Secondary Outcome Measures
Name Time Method <p>PK Parameters:<br /><br>- Dextromethorphan and dextrophan: T1/2, Tmax, apparent clearance (CL/F), and<br /><br>terminal elimination rate constant (kel)<br /><br>- Rosuvastatin: T1/2, Tmax, kel, CL/F<br /><br>Endpoints for safety and tolerability assessment when emvododstat is<br /><br>administered in combination with a CYP2D6 (dextromethorphan) and BCRP<br /><br>(rosuvastatin) substrates:<br /><br>- Adverse events<br /><br>- Chemistry and hematology laboratory panels<br /><br>- 12 lead ECGs<br /><br>- Vital signs<br /><br>- Physical examinations</p><br>