Clinical trial NCT06411860: A Study to Assess the Effect of Olpasiran on QT/QTc Intervals in Healthy Participants
Official title: A Randomized, Placebo- and Positive-controlled, Crossover Study to Assess the Effect of Olpasiran (AMG 890) on QT/QTc Intervals in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Basic Science
Keywords: QT/QTc Intervals
Healthy Participants
Olpasiran
AMG 890
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2024-05-13
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Placebo-corrected Change From Baseline in QT Corrected for Heart Rate (HR) Interval Based on the Fridericia Correction (QTcF) (ΔΔQTcF) After Olpasiran Dosing
timeFrame: Day 3 of Treatment Period 4 (up to approximately 9.5 weeks)
Secondary outcomes:
measure: Maximum Observed Concentration (Cmax) of Olpasiran
timeFrame: Up to 10 weeks
measure: Time to Cmax (tmax) of Olpasiran
timeFrame: Up to 10 weeks
measure: Half-life of Olpasiran (t1/2)
timeFrame: Up to 10 weeks
measure: Area Under the Curve From Time 0 to the Last Quantifiable Concentration (AUClast)
timeFrame: Up to 10 weeks
measure: Area Under the Curve From Time 0 to Infinity (AUCinf)
timeFrame: Up to 10 weeks
measure: Change From Baseline in HR
timeFrame: Up to 10 weeks
measure: Change From Baseline in QTcF
timeFrame: Up to 10 weeks
measure: Change From Baseline in PR Interval
timeFrame: Up to 10 weeks
measure: Change From Baseline in QRS Interval
timeFrame: Up to 10 weeks
measure: Placebo-corrected Change From Baseline in HR
timeFrame: Up to 10 weeks
measure: Placebo-corrected Change From Baseline in PR Interval
timeFrame: Up to 10 weeks
measure: Placebo-corrected Change From Baseline in QRS Interval
timeFrame: Up to 10 weeks
measure: Number of Participants with Categorical Outliers Related to the Following ECG parameter: QTcF, HR, PR, and QRS
timeFrame: Up to 10 weeks
measure: Frequency of Treatment-emergent Changes in Electrocardiogram (ECG) Morphology
timeFrame: Up to 10 weeks
measure: ΔΔQTcF After Moxifloxacin Dosing
timeFrame: Up to 10 weeks
measure: Number of Participants With Treatment-emergent Adverse Events
timeFrame: Up to 10 weeks
measure: Number of Participants With Treatment-emergent Serious Adverse Events
timeFrame: Up to 10 weeks
Other outcomes:
Locations:
city: Leeds
country: United Kingdom
facility: Fortrea Clinical Research Unit Limited - Leeds
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: