A Study to Assess the PK, PD, Safety and Tolerability of Eplontersen in Healthy Chinese Volunteers
- Conditions
- Transthyretin-mediated Amyloidosis
- Registration Number
- NCT06527755
- Lead Sponsor
- AstraZeneca
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 12
Inclusion Criteria:<br><br> 1. Must have given written informed consent (signed and dated) and any authorizations<br> required by local law and be able to comply with all study requirements.<br><br> 2. Healthy* Chinese males or females of non-childbearing potential, aged 18 to 60<br> inclusive at the time of informed consent.<br><br> Participants will be confirmed to be healthy according to the medical history,<br> electrocardiogram (ECG), vital signs, laboratory results, and physical examination<br> as determined by the Investigator.<br><br> 3. Females must be non-pregnant and non-lactating, and either surgically sterile (eg,<br> tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy) or<br> postmenopausal (defined as 12 months of spontaneous amenorrhea without an<br> alternative medical cause and follicle-stimulating hormone (FSH) levels in the<br> postmenopausal range for the laboratory involved. Males must be surgically sterile<br> or abstinent, or if engaged in sexual relations with a female of child-bearing<br> potential, the participant must be using an highly effective contraceptive method<br> from the time of signing the informed consent form until at least 24 weeks after<br> study intervention administration.<br><br> * Abstinence is only acceptable as true abstinence, ie, when this is in line with<br> the preferred and usual lifestyle of the participant. Periodic abstinence (eg,<br> calendar, ovulation, symptothermal, post-ovulation methods), declaration of<br> abstinence for the duration of a study and withdrawal are not acceptable methods of<br> contraception.<br><br> 4. Willing to refrain from strenuous exercise/activity (eg, heavy lifting, weight<br> training, intense aerobics classes) for at least 72 hours prior to study visits.<br><br> 5. Weight = 50 kg and body mass index (BMI) of 19 to 30 kg/m2 at screening (including<br> cutoff).<br><br> BMI = weight (kg)/height2 (m2).<br><br> 6. Willingness to take vitamin A supplements (recommended daily allowance [RDA] of<br> approximately 3000 IU/day until the last post-treatment follow-up visit [Day 92; 13<br> weeks after the dosing]).<br><br>Exclusion Criteria:<br><br> 1. Clinically significant abnormalities in medical history (eg, major surgery within 6<br> months of screening, history or presence of hepatic, renal, hematological,<br> endocrine, or cardiovascular disease) or physical examination.<br><br> 2. Screening laboratory results as follows, or any other clinically significant<br> abnormalities in screening laboratory values that would render a participant<br> unsuitable for inclusion:<br><br> - Random spot urine protein/creatinine ratio (UPCR) = 200 mg/g. In the event of<br> UPCR above this threshold ineligibility may be confirmed by a repeat random<br> spot UPCR = 200 mg/g or a 24-hour urine protein = 200 mg/24 hour;<br><br> - Positive test for blood (including trace) on urinalysis that is subsequently<br> confirmed with urine microscopy showing > 5 red blood cells per high power<br> field;<br><br> - Alanine transaminase (ALT), aspartate aminotransferase (AST), bilirubin,<br> alkaline phosphatase (ALP), serum creatinine, and blood urea > upper limit of<br> normal (ULN);<br><br> - Fasting blood glucose > ULN;<br><br> - Platelet count < lower limit of normal (LLN);<br><br> - Estimated glomerular filtration rate (eGFR) (Chronic Kidney Disease<br> Epidemiology Collaboration [CKD-EPI] equation) = 60 mL/min/1.73m2.<br><br> 3. Active infection requiring systemic antiviral or antimicrobial therapy that will not<br> be completed prior to Day 1.<br><br> 4. Unwillingness to comply with study procedures, including follow-up, as specified by<br> this protocol, or unwillingness to cooperate fully with the Investigator.<br><br> 5. Known history of or positive test for human immunodeficiency virus (HIV), hepatitis<br> B antigen, and hepatitis C antibody.<br><br> 6. Uncontrolled hypertension (systolic blood pressure [BP] > 160 mmHg, or diastolic BP<br> > 100 mmHg).<br><br> 7. Malignancy within 5 years, except for basal or squamous cell carcinoma of the skin<br> or carcinoma in situ of the cervix that has been successfully treated.<br><br> 8. Treatment with another investigational drug, biological agent, or device within 1<br> month of screening, or 5 half-lives of study intervention, whichever is longer.<br><br> 9. Previous treatment with an oligonucleotide (including small interfering ribonucleic<br> acid) within 4 months of screening if single dose received, or within 12 months of<br> screening if multiple doses received (exception for SARS-Cov2 vaccines [both mRNA<br> and viral vector vaccines]; any vaccine should be administered at least 7 days prior<br> to study intervention).<br><br> 10. History of bleeding diathesis or coagulopathy.<br><br> 11. Regular use of alcohol within 6 months prior to screening (> 7 drinks/wk for<br> females, > 14 drinks/wk for males [1 drink = 5 ounces (150 mL) of wine or 12 ounces<br> (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor]), or use of soft drugs (such<br> as marijuana) within 3 months prior to screening, or hard drugs (such as cocaine and<br> phencyclidine) within 1 year prior to screening, or positive urine drug and alcohol<br> screen at screening.<br><br> 12. Concomitant medication restrictions including any prescription and over-the-counter<br> (OTC) and herbal remedies, other than occasional acetaminophen (paracetamol) or<br> ibuprofen unless authorized by the Study Clinical Lead.<br><br> 13. Smoking limitations: smoking > 10 cigarettes a day.<br><br> 14. Blood donation of 50 to 499 mL within 30 days of screening or of > 499 mL within 60<br> days of screening.<br><br> 15. Have any other conditions, which, in the opinion of the Investigator or Sponsor<br> would make the participant unsuitable for inclusion, or could interfere with the<br> participant participating in or completing the study.
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method PK parameters: Maximum Observed Concentration(Cmax);PK parameters: Time to Maximal Concentration (tmax);PK parameters: Plasma Half-life Associated with the Apparent Terminal Elimination Phase (t½?z);PK parameters: Area Under Plasma Concentration-time Curve (0-24 hours) (AUC0-24h);PK parameters: Area Under Plasma Concentration-time Curve (0-168 hours) (AUC0-168h)
- Secondary Outcome Measures
Name Time Method The change and percent change from baseline in serum (Transthyretin) TTR levels at specified timepoints