A Phase 1, Randomized, Double-Blind, Placebo- and Positive-Controlled, Parallel-Group Study to Evaluate the Effect of LMTM on the Response to an Oral Tyramine Challenge and to Determine the Multiple-Dose Pharmacokinetics of LMTM.
- Conditions
- Alzheimers Diseasethinking and behaviortype of dementia that affects memory10042258
- Registration Number
- NL-OMON51826
- Lead Sponsor
- TauRx Therapeutics Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 120
1. Signature of an Independent Ethics Committee approved written informed
consent prior to any clinical study-related procedures.
2. Male or female subjects
2.1. Aged 18 to 60 years, inclusive (Tyramine Challenge Parts 1 and 2);
2.1.1. The goal will be to enroll approximately 12 or more subjects aged >=50
years in each part.
2.2. Aged >=50 years (PK Substudy).
3. Weighing between 50 and 110 kg, inclusive such that the body mass index
(BMI) is 18.5 to 32 kg/m2, inclusive.
4. In good health in the opinion of the PI as determined by:
4.1. Medical history;
4.2. Physical examination;
4.3. Vital signs assessment;
4.4. 12-lead electrocardiogram (ECG); and
4.5. Clinical laboratory evaluations.
5. If female, must meet one of the following:
5.1. Be permanently sterile, defined as at least 6 months following
hysterectomy, bilateral salpingectomy, or bilateral oophorectomy.
5.2. Have undergone bilateral tubal occlusion / ligation at least 6 months
prior to screening.
5.3. Be postmenopausal, defined as at least 12 months post cessation of menses
(without an alternative medical cause); postmenopausal status will be confirmed
with a screening serum follicle stimulating hormone (FSH) level greater than
33.4 mIU/mL.
5.4. Using adequate contraception and agree to do so throughout study
participation and for 90 days after the last dose of study drug; the following
are considered effective forms of birth control:
5.4.1. Hormonal contraceptives started at least 90 days prior to study drug
administration;
5.4.2. Intra-uterine contraceptive device (hormonal or non-hormonal) placed at
least 4 weeks prior to study drug administration;
5.4.3. Male condom;
5.4.4. Sterile male partner (vasectomized for at least 6 months); and
5.4.5. True abstinence (when this is in line with the preferred and usual
lifestyle of the subject).
6. If female, including those who have underwent hysterectomy, must agree to
not donate ova starting from Day -1 and throughout the clinical study period,
and for at least 28 days after the final study drug administration.
7. If male and sexually active with a female partner of childbearing potential
(childbearing potential females are defined as women who are neither
postmenopausal nor surgically sterile), must be willing to use one of the
following acceptable contraceptive methods from the first study drug
administration until at least 90 days after the last study drug administration:
7.1. Simultaneous use of a male condom and, for the female partner, hormonal
contraceptives used since at least 4 weeks or intra-uterine contraceptive
device placed since at least 4 weeks;
7.2. Simultaneous use of a male condom and, for the female partner, a diaphragm
or cervical cap.
8. If male, must agree to not donate sperm from Day -1 until 90 days after the
final study drug administration.
1. If female, pregnant or lactating.
2. History of allergy/sensitivity to the following:
2.1. Phenelzine, selegiline, or other drugs of a similar class (Tyramine
Challenge Parts 1 and 2 only).
2.2. Methylthioninium (methylene blue) or similar organic dyes, as determined
by the PI.
2.3. Any of the excipients used in LMTM (which include mannitol, cellulose,
crospovidone, and magnesium stearate).
3. Clinically significant history of allergic conditions (including severe
hypersensitivity drug reactions, asthma, eczema or anaphylactic reactions, but
excluding untreated, asymptomatic seasonal allergies at the time of dosing), as
judged by the PI.
4. For Tyramine Challenge Parts 1 and 2 only, subject is unable to swallow the
capsule sizes used in this study.
5. Febrile illness or symptomatic viral, bacterial (including upper respiratory
infection), or fungal (noncutaneous) infection within 1 week prior to admission
to the clinical unit.
Further criteria apply, see protocol.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>To determine whether LMTM inhibits MAO as evidenced by a reduction in the dose<br /><br>of tyramine required to produce a 30-mmHg increase in systolic blood pressure<br /><br>(SBP), compared with placebo.</p><br>
- Secondary Outcome Measures
Name Time Method <p>- To characterize the multiple-dose pharmacokinetics (PK) of LMTM.<br /><br><br /><br>- To assess the safety and tolerability of LMTM.</p><br>