A PHASE I, DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED, MULTICENTER, SINGLE- AND MULTIPLE-ASCENDING-DOSE STUDY TO DETERMINE INITIAL SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF GDC-0134 IN PATIENTS WITH AMYOTROPHIC LATERAL SCLEROSIS
- Conditions
- Amyotrophic lateral sclerosisneurodegenerative disease10029317
- Registration Number
- NL-OMON46763
- Lead Sponsor
- Genentech, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Withdrawn
- Sex
- Not specified
- Target Recruitment
- 6
Inclusion criteria for study entry are as follows:
* Signed Informed Consent Form
* Age * 18 years
* Able to comply with the study protocol, in the investigator*s judgment
* Male or female participants with a diagnosis of possible, laboratory-supported probable, probable, or definite ALS according to modified El Escorial criteria
* For men: agreement to remain abstinent or use a condom during the treatment period and for at least 90 days after the last dose of study drug and agreement to refrain from donating sperm during this same period ;Men who wish to father a child should consider sperm banking prior to entry into the study.
Men with a pregnant partner must agree to remain abstinent or use a condom for the duration of the pregnancy.
Abstinence is acceptable only if it is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
* For women who are not postmenopausal (* 12 months of non*therapy-induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent or use two adequate methods of contraception, including at least one method with a failure rate of < 1% per year, during the treatment period and for at least 28 days after the last dose of study drug ;Abstinence is acceptable only if it is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
Barrier methods must always be supplemented with the use of a spermicide.
Examples of contraceptive methods with a failure rate of < 1% per year include tubal ligation, male sterilization, hormonal implants, established, proper use of combined oral or injected hormonal contraceptives, and certain intrauterine devices.
Hormonal contraceptive methods must be supplemented by a barrier method.
* Ability to swallow up to 12 capsules with water and ingest approximately 120 mL (4 ounces) of applesauce containing drug suspension within 5 minutes during each dosing period
* Upright forced vital capacity of at least 50%
* Ability to fast from food for 8 hours prior to dosing and 2 hours after dosing
Patients who meet any of the following criteria will be excluded from study entry:
* Pregnant or lactating or intending to become pregnant ;Women who are not postmenopausal (* 12 months of non*therapy-induced amenorrhea) or surgically sterile must have a negative serum pregnancy test result within 28 days prior to initiation of study drug and a negative urine pregnancy test on Day * 1 (if positive, this should be confirmed with a serum pregnancy test).
* Best-corrected visual acuity worse than 20/40 in either eye
* History of optic neuropathy
* History of optic disc swelling or atrophy
* History of intraocular eye disease (e.g., glaucoma, uveitis, diabetic retinopathy)
* History of intraocular surgery or retinal laser treatment, with the exception of cataract surgery > 3 months before Day * 1 ;YAG laser capsulotomy is allowed if not within 3 months of Day *1.
* Poorly controlled diabetes ;If there is a medical history of diabetes or if the investigator suspects that diabetes is present, hemoglobin A1C should be reviewed in the patient*s medical record or, if no recent value is available, obtained at screening; a value * 8% constitutes poor control
* Presence of cognitive impairment, clinical dementia, or psychiatric illness, or other neurodegenerative disease (e.g., Parkinson*s disease or Alzheimer*s disease) that is significant, in the opinion of the investigator
* Currently taking riluzole unless on a stable dose for the 3 months prior to Day -1 and without current liver enzyme or liver function abnormalities
* Currently taking edaravone unless after completion of at least the second 14-day drug-treatment period, as long as Day 1 occurs during a drug-free period at least 24 hours after the last edaravone dose and at least 5 days prior to the first dose of the next cycle.
* Currently taking medications with significant risk of producing liver injury (e.g., statins, creatine) unless on a stable dose for the 6 months prior to screening and without a history of liver enzyme or liver function abnormalities
* Currently taking nutritional/herbal supplements (except for over-the-counter vitamins that are within Recommended Dietary Allowance [RDA]) unless discontinued at least 7 days prior to Day * 1, except upon approval of both the investigator and Sponsor. ;No new nutritional/herbal supplement may be initiated during the study.
* Investigational therapy within 1 month or 5 half-lives, whichever is longer, prior to initiation of study treatment ;This criterion applies equally to GDC-0134, in the case of a patient from the SAD stage of the study who rescreens for the MAD stage of the study.
* Currently taking anticoagulation medications, including low molecular heparin, non*vitamin K antagonist oral anticoagulants (NOACs), antiplatelet therapy (e.g., Plavix [clopidogrel]) ;Aspirin and other non-steroidal anti-inflammatory drugs are allowed.
The use of heparin to maintain patency of intravenous (IV) catheters is allowed, because it is not expected to affect the coagulation status of the patient.
* Planned parenteral feeding tube placement during the study
* Positive for hepatitis C antibody, hepatitis B surface antigen, or HIV antibody
* History of illicit drug or alcohol abuse within 12 months prior to screening, in the investigator*s judgment
* Serious infection requiring oral or IV antibiotics within 30 days prior to screening
* Any medical condition or clini
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>* Incidence, nature, and severity of all adverse events<br /><br>* Incidence and nature of laboratory abnormalities, based on hematology,<br /><br>clinical chemistry, urinalysis, and fecal occult blood test results<br /><br>* Changes in vital signs and ECGs<br /><br>* Physical examination findings, especially neurological and ophthalmological<br /><br>findings</p><br>
- Secondary Outcome Measures
Name Time Method <p>* Time to maximum plasma concentration (tmax)<br /><br>* AUC<br /><br>* Apparent clearance (CL/F)<br /><br>* Apparent terminal volume of distribution (Vz/F)<br /><br>* Apparent t1/2<br /><br>* PK-dose proportionality as assessed with Cmax and AUC<br /><br>* Accumulation ratio</p><br>