Basic Science
Conditions
Keywords
QT/QTc Intervals, Healthy Participants, Olpasiran, AMG 890
Brief summary
The primary objective of the study is: • To assess the effects of a single therapeutic and supratherapeutic dose of olpasiran on the placebo-corrected change from baseline in QT corrected for heart rate (ΔΔQT)/QTc interval in healthy participants.
Interventions
OTHERPlacebo
Participants will receive a subcutaneous (SC) injection of placebo.
DRUGOlpasiran
Participants will receive a SC injection of olpasiran at dose level 1 or 2.
DRUGMoxifloxacin
Participants will receive a single dose of moxifloxacin as an oral tablet by mouth.
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Provide informed consent prior to starting study activities. * Healthy male or female participants, between 18 and 60 years of age (inclusive) at the time of Screening. Females must be of nonchildbearing potential. * Body mass index between 18 and 30 kg/m\^2 (inclusive) at the time of Screening. Participants must have a body mass ≥ 50kg.
Exclusion criteria
* History or evidence, at Screening or Check-in, of clinically significant disorder, condition, or disease not otherwise excluded that, in the opinion of the Investigator (or designee), would pose a risk to participant safety or interfere with the study evaluation, procedures, or completion. * History or current signs or symptoms of cardiovascular disease, including but not limited to myocardial infarction, congenital heart disease, valvular heart disease coronary revascularization, or angina. * History or evidence of clinically significant arrhythmia at screening, including any clinically significant findings on the ECG taken at Check-in. * Systolic blood pressure \> 150 mmHg or \< 90 mmHg, or diastolic blood pressure \> 90 mmHg or \< 50 mmHg, or HR ≤ 40 and \> 100 bpm, at Screening or Check-in; one repeat blood pressure measurement will be allowed at Screening and Check-in. * History suggestive of esophageal (including esophageal spasm, esophagitis), gastric, or duodenal ulceration or bowel disease (including but not limited to peptic ulceration, gastrointestinal bleeding, ulcerative colitis, Crohn's disease, or irritable bowel syndrome), or a history of gastrointestinal surgery other than uncomplicated appendectomy and hernia repair. * Inability to swallow oral medication or history of malabsorption syndrome. * History of hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee) and in consultation with the Sponsor. * History of major bleeding disorder (for example: hemophilia, von Willebrand disease, clotting factor deficiencies, etc). * Participant has received a dose of an investigational drug within the past 90 days or have previously completed or withdrawn from this study or any other study investigating olpasiran or have previously received olpasiran.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Placebo-corrected Change From Baseline in QT Corrected for Heart Rate (HR) Interval Based on the Fridericia Correction (QTcF) (ΔΔQTcF) After Olpasiran Dosing | Day 3 of Treatment Period 4 (up to approximately 9.5 weeks) |
Secondary
| Measure | Time frame |
|---|---|
| Time to Cmax (tmax) of Olpasiran | Up to 10 weeks |
| Half-life of Olpasiran (t1/2) | Up to 10 weeks |
| Area Under the Curve From Time 0 to the Last Quantifiable Concentration (AUClast) | Up to 10 weeks |
| Area Under the Curve From Time 0 to Infinity (AUCinf) | Up to 10 weeks |
| Change From Baseline in HR | Up to 10 weeks |
| Change From Baseline in QTcF | Up to 10 weeks |
| Change From Baseline in PR Interval | Up to 10 weeks |
| Change From Baseline in QRS Interval | Up to 10 weeks |
| Maximum Observed Concentration (Cmax) of Olpasiran | Up to 10 weeks |
| Placebo-corrected Change From Baseline in PR Interval | Up to 10 weeks |
| Placebo-corrected Change From Baseline in QRS Interval | Up to 10 weeks |
| Number of Participants with Categorical Outliers Related to the Following ECG parameter: QTcF, HR, PR, and QRS | Up to 10 weeks |
| Frequency of Treatment-emergent Changes in Electrocardiogram (ECG) Morphology | Up to 10 weeks |
| ΔΔQTcF After Moxifloxacin Dosing | Up to 10 weeks |
| Number of Participants With Treatment-emergent Adverse Events | Up to 10 weeks |
| Number of Participants With Treatment-emergent Serious Adverse Events | Up to 10 weeks |
| Placebo-corrected Change From Baseline in HR | Up to 10 weeks |
Countries
United Kingdom
Outcome results
None listed