A Study to Assess the Effect of Olpasiran on QT/QTc Intervals in Healthy Participants

A Randomized, Placebo- and Positive-controlled, Crossover Study to Assess the Effect of Olpasiran (AMG 890) on QT/QTc Intervals in Healthy Subjects

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Basic Science
• Intervention / Treatment: Other: Placebo; Drug: Olpasiran; Drug: Moxifloxacin

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Amgen Call Center; Phone Number: 866-572-6436; Email: medinfo@amgen.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Treatment A; All participants will be randomized to 1 of 12 treatment sequences and receive a single dose of one of the following treatments, according to the randomization schedule: Treatment A: placebo Treatment B: dose level 1 olpasiran Treatment C: dose level 2 olpasiran Treatment D: moxifloxacin	Other: Placebo; Participants will receive a subcutaneous (SC) injection of placebo.
Experimental: Treatment B; All participants will be randomized to 1 of 12 treatment sequences and receive a single dose of one of the following treatments, according to the randomization schedule: Treatment A: placebo Treatment B: dose level 1 olpasiran Treatment C: dose level 2 olpasiran Treatment D: moxifloxacin	Drug: Olpasiran; Participants will receive a SC injection of olpasiran at dose level 1 or 2.
Experimental: Treatment C; All participants will be randomized to 1 of 12 treatment sequences and receive a single dose of one of the following treatments, according to the randomization schedule: Treatment A: placebo Treatment B: dose level 1 olpasiran Treatment C: dose level 2 olpasiran Treatment D: moxifloxacin	Drug: Olpasiran; Participants will receive a SC injection of olpasiran at dose level 1 or 2.
Active Comparator: Treatment D; All participants will be randomized to 1 of 12 treatment sequences and receive a single dose of one of the following treatments, according to the randomization schedule: Treatment A: placebo Treatment B: dose level 1 olpasiran Treatment C: dose level 2 olpasiran Treatment D: moxifloxacin	Drug: Moxifloxacin; Participants will receive a single dose of moxifloxacin as an oral tablet by mouth.

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	Time Frame
Maximum Observed Concentration (Cmax) of Olpasiran	Up to 10 weeks
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
Placebo-corrected Change From Baseline in HR	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

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Estimated): August 8, 2024
• Primary Completion (Estimated): October 28, 2024
• Study Completion (Estimated): October 28, 2024

Study Registration Dates

• First Submitted: April 29, 2024
• First Submitted That Met QC Criteria: May 10, 2024
• First Posted (Actual): May 13, 2024

Study Record Updates

• Last Update Posted (Actual): May 13, 2024
• Last Update Submitted That Met QC Criteria: May 10, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Healthy Participants; Olpasiran; AMG 890; QT/QTc Intervals
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Moxifloxacin
• Other Study ID Numbers: 20220016

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• IPD Sharing Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No