Eligibility Details:
Inclusion Criteria
1. Must have given written informed consent (signed and dated) and any authorizations
required by local law and be able to comply with all study requirements
2. Healthy Japanese males or females of non-childbearing potential, aged 20 to 65
inclusive at the time of informed consent defined as being of first- or
second-generation ethnic origin with each set of parents qualifying as Japanese under
the prior generation. Generations will be defined as follows:
- First generation Japanese participants must be born in Japan, cannot have lived
outside of Japan for more than 10 years, must maintain Japanese diet, culture and
lifestyle and parents and both sets of grandparents are of Japanese origin
- Second-generation Japanese are participants who are born outside of Japan to the
first-generation Japanese parents
3. Females must be non-pregnant and non-lactating, and either surgically sterile (e.g.,
tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy) or
post-menopausal (defined as 12 months of spontaneous amenorrhea without an alternative
medical cause and follicle-stimulating hormone (FSH) levels in the postmenopausal
range for the laboratory involved Males must be surgically sterile or abstinent*, if
engaged in sexual relations with a female of child-bearing potential, the participant
must be using an acceptable contraceptive method from the time of signing the informed
consent form until at least 91 days (single-dose cohorts) or 13 weeks (multiple-dose
cohorts) after the last dose of Study Drug (AKCEA-TTR-LRx or placebo)
* Abstinence is only acceptable as true abstinence, i.e., when this is in line with
the preferred and usual lifestyle of the participant. Periodic abstinence (e.g.,
calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence
for the duration of a trial and withdrawal are not acceptable methods of
contraception.
4. Willingness to take vitamin A supplements
Exclusion Criteria
1. Clinically significant abnormalities in medical history (e.g., previous acute coronary
syndrome within 6 months of Screening, major surgery within 3 months of Screening) or
physical examination
2. Screening laboratory results as follows, or any other clinically significant
abnormalities in Screening laboratory values that would render a participant
unsuitable for inclusion
- Random spot urine protein/creatinine (P/C) ratio (UPCR) ≥ 200 milligrams per gram
(mg/g).
- Alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin,
alkaline phosphatase (ALP), serum creatinine, blood urea nitrogen (BUN) > upper
limit of normal (ULN)
- Fasting blood glucose > ULN
- Platelet count < lower limit of normal (LLN)
3. Uncontrolled hypertension (blood pressure [BP] > 160/100 millimeters of mercury [mm
Hg])
4. Malignancy within 5 years, except for basal or squamous cell carcinoma of the skin or
carcinoma in situ of the cervix that has been successfully treated
common.study.methods.has-drugs-yes
common.study.methods.is-healthy-no
