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A Study to Assess the Safety, Tolerability, and Pharmacology of Darifenacin in Patients With ALS
Bu çalışma, amiyotrofik lateral skleroz (amyotrophic lateral sclerosis, ALS) hastalarında Darifenacin adlı ilacın güvenliliğini, tolere edilebilirliğini ve vücuttaki etkilerini değerlendirmektedir. Çalışmaya, ailesel veya sporadik ALS tanısı doğrulanmış, belirtileri 36 aydan kısa süredir devam eden, 18-85 yaş arası hastalar alınmaktadır. Çalışma Faz 2 aşamasında yürütülmekte ve halen katılımcı almaktadır.
Yukarıdaki özet, resmî kaydın sade dile aktarılmış halidir. Orijinal İngilizce başlık referans için gösterilir.
Kriterler ClinicalTrials.gov kaydından orijinal İngilizce haliyle alınmıştır. Uygunluk kararını yalnızca deneyi yürüten ekip verebilir.
Inclusion Criteria:
1. Able to comprehend and willing to sign an Informed Consent Form (ICF).
2. Male or female, ≥ 18 years old and ≤85 years old, at the time of signing the ICF.
3. Confirmed diagnosis of familial or sporadic ALS, defined as meeting the probable, laboratory-supported probable, or definite criteria for a diagnosis of ALS according to the World Federation of Neurology Modified El Escorial criteria (1).
4. ALS duration of less than 36 months from the symptom onset.
5. FVC of ≥ 50 %.
6. Able to swallow tablets without crushing.
7. A female patient is eligible to participate if she is not breastfeeding, has negative pregnancy test at screening, has no intention of becoming pregnant during the course of the study, and agrees to use appropriate contraceptive drugs or devices (as defined in section 3.4 of the study protocol) for the duration of the study.
8. If male and has a partner who may become pregnant, agrees to ensure that he and/or his partner use a reliable form of birth control (as defined in section 3.4 of the study protocol) for the duration of the study and refrain from donating sperm during this period.
9. Participants receiving standard care for ALS prior to entering the trial (i.e. Riluzole, Edaravone, and Albrioza), must be on a stable dosing regimen prior to the randomization and agree to remain on this dosage during the study period:
* In the case of taking Riluzole, the patient must have been on a stable dose at least 30 days prior to start date.
* In the case of taking Edaravone, the patient must have been on a stable dose at least 30 days prior to start date.
* In the case of receiving Albrioza, the patient must have been on a stable dose at least 30 days prior to start date.
10. For participants who consent to the optional biopsy:
* Participants with normal platelet or coagulation test values.
* Participants who are receiving anticoagulant medications will need to abstain from using anticoagulants for a specific number of days before and after the biopsy, as decided by the study doctor on a case-by-case basis.
Exclusion Criteria:
1. Patients with, or at risk for, the following conditions:
* Untreated or uncontrolled narrow-angle glaucoma;
* Gastric retention
* Urinary retention
* Liver disease
2. Patients with a known history of severe allergic or anaphylactic reactions to antimuscarinic medications
3. If diagnosed with another neurodegenerative disease (e.g. Multiple Sclerosis, Parkinson, Myasthenia Gravis, and Alzheimer's disease).
4. Subjects with severe hepatic impairment or abnormal liver enzymes, as defined as Child-Pugh B and C scores.
5. Subject has a history of, or positive test result at Screening, for hepatitis C virus antibody.
6. Subjects with acute or prolonged hepatitis B \& C.
7. Any medical condition that might interfere with the patient's participation in the trial, poses any added risk for the patient, or confounds the assessment of the patient according to the Investigator's judgement.
8. Subjects with any uncontrolled (unresolved) medical condition other than ALS, as determined by the Investigator.
9. Subjects who are currently enrolled in another clinical trial and receiving an Investigational Product (IP) (including but not limited to stem cell therapy or gene therapy).
10. Treatment with an investigational drug within 1 month or within a time period equal to 5 half-lives (if known) whichever is longer, of starting study treatment.
11. Patients with prior darifenacin treatment.
12. History of drug and/or alcohol abuse (according to Diagnostic and Statistical Manual of Mental Disorders) prior to the screening as determined by the Investigator.
13. If female, subjects who are pregnant, breastfeeding, or intending to conceive during the course of the study.
14. Subjects with an abnormal electrocardiogram (ECG) at screening (any abnormality that the PI believes that entering the study place the participant at risk).
15. Subjects who are receiving strong CYP3A4 inducers such as carbamazepine (anticonvulsant), phenytoin (anticonvulsant), rifampin (antibiotic), and modafinil (wakefulness-promoting agent).
16. Subjects who are receiving potent CYP3A4 inhibitors such as clarithromycin (macrolide antibiotic), ketoconazole and itraconazole (antifungal medications), nefazadone (antidepressant), nelfinavir and ritonavir (protease inhibitors).
17. Subjects who are receiving or received within 30 days prior to the starting of the trial CYP2D6 substrates with a narrow therapeutic window such as include flecainide (Class IC anti-arrhythmic), thioridazine (antipsychotic) and tricyclic antidepressants.
18. Subjects who are receiving or received botulinum injections in the past 6 months.
19. Subjects who are receiving or received within 30 days prior to the starting of the trial antimuscarinic medications for the treatment of overactive bladder such as fesoterodine, oxybutynin, solifenacin, tolterodine, and trospium.
20. Only for patients that consented to the Optional Needle Muscle Biopsy procedures.
21. Subject is taking an anticoagulant (with the exception of aspirin at the investigator's discretion) or is at risk of increased or uncontrolled muscle biopsy-related bleeding.
22. Subjects with bleeding risk factors which include, but are not limited to, anatomical factors at or near the muscle biopsy site (e.g., vascular abnormalities, neoplasms, or other abnormalities) or abnormal platelet or coagulation test values at visit 1.