E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Prevention of migraine headaches |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10027599 |
E.1.2 | Term | Migraine |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the effect of AMG 334 compared to placebo on exercise capacity in subjects with stable angina as measured by total exercise time (TET) during an exercise treadmill test (ETT). |
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E.2.2 | Secondary objectives of the trial |
To evaluate the effect of AMG 334 compared to placebo during an ETT on the time to the onset of:
• Exercise-induced angina
• ST-segment depression |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Subject has provided informed consent/assent prior to initiation of any study-specific activities/procedures.
• Age ≥ 18 to ≤ 85 at the time of screening.
• History of chronic stable angina for at least 3 months prior to screening, with at least 1 angina episode/month, on average over that period.
• Ischemic heart disease documented by any one or more of the following:
a. A history of myocardial infarction (MI) with elevated Creatine kinase - myocardial band (CK-MB), troponin I or T, or the presence of electrocardiogram (ECG) changes consistent with an MI, or
b. Coronary angiography demonstrating at least 1 major epicardial coronary artery (eg, left anterior descending, left circumflex, or right coronary artery) with a stenosis of at least 50% diameter or greater but excluding > 50% or flow-limiting stenosis of the left main coronary artery unless revascularized by coronary artery bypass grafting, or
c. Revascularization procedure (eg, cardiac bypass graft, angioplasty) ≥ 3 months prior to screening
• Receiving stable doses of cardiac medications (eg, beta blockers, calcium channel blockers, antianginals, etc.) for at least 30 days prior to randomization and that are not expected to change during the study
• Completes 2 consecutive ETTs during screening, performed > 48 hours and ≤ 14 days apart using a standard Bruce ETT protocol, with:
a. Limitation of exercise due to symptoms of angina or ≥ 3 mm ST-segment depression
b. ≥ 1.0 mm ischemic ST-segment depression
c. Exercise duration of ≥ 3 to ≤ 12 minutes , and
d. ≤ 1 minute difference or within 20% duration (using the longest duration qualifying ETT) in TET between the 2 qualifying tests
e. ECG tracings from screening ETTs are acceptable to the core ECG laboratory
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E.4 | Principal exclusion criteria |
General
• Currently participating in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug studies. Other investigational procedures while participating in this study are not allowed.
• Current or prior malignancy within 5 years of randomization, with the exception of non-melanoma skin cancers, cervical or breast ductal carcinoma in situ, and adenocarcinoma of the prostate Stage I or IIa (defined as T1, T2a or T2b, N0, M0 with documented serum PSA <20ng/mL and Gleason score ≤7) per the American Joint Committee on Cancer (AJCC) primary tumor, regional lymph nodes, and distant metastasis system.
• Subject has known sensitivity to any of the components of the investigational product
• Subject likely to not be available to complete all protocol-required study visits or procedures, and/or not adequately comply with all required study procedures
• History or evidence of clinically significant disorder, condition or disease that may pose a risk to subject safety or interfere with the study evaluation, procedures or completion
Reproductive
Females of reproductive potential who are not willing to use highly effective methods of birth control during treatment with AMG 334 and for an additional 12 weeks after receiving a single dose of AMG 334
• Highly effective methods of contraception as per Clinical Trial
Facilitation Group recommendations include:
• Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:
o oral
o intravaginal
o transdermal
• Progestogen-only hormonal contraception associated with inhibition of ovulation:
o oral
o injectable
o implantable
• Intrauterine device (IUD)
• Intrauterine hormone-releasing system (IUS)
• Bilateral tubal occlusion
• Vasectomized partner (with medical assessment of the surgical success of this procedure)
• Sexual abstinence
• Female subjects not of childbearing potential are defined as: Any female who is has had a hysterectomy, OR bilateral
salpingectomy, OR bilateral oophorectomy, OR are post-menopausal.
Post-menopausal women are those who fit into one of the following categories:
o Age 55 years with cessation of menses for 12 or more months, OR
o Age < 55 years but no spontaneous menses for at least 2 years, OR
o Age < 55 years and spontaneous menses within the past 1 year, but currently amenorrheic (eg, spontaneous or secondary to hysterectomy), AND with postmenopausal gonadotropin level (luteinizing hormone and follicle-stimulating hormone levels > 40 IU/L) or postmenopausal
estradiol levels (< 5 ng/dL) or according to the definition of "postmenopausal range" for the laboratory involved.
• Females who are pregnant, planning to become pregnant, or breastfeeding during treatment with AMG 334 and for an additional 12 weeks after receiving a single dose of AMG 334.
• Subject with a positive pregnancy test at screening
Psychiatric and Neurologic
• Within the 6 months prior to or during screening, report of suicidal ideation with intent, with or without a plan, or suicidal behavior as evidenced by a Columbia-Suicide Severity Rating Scale (C-SSRS) > 2 during screening.
• Any psychiatric or neurologic conditions that may interfere with the conduct of the study.
Psychosocial
•History of alcohol abuse or dependence within 12 months prior to study enrollment, or inability to refrain from alcohol use within 8 hours prior to ascheduled ETT.
• Inability to refrain from use of caffeine or nicotine products within 2 hours prior to a scheduled ETT.
• Unable to refrain from unaccustomed strenuous physical activity from the date of consent through their completion of the trial.
Cardiovascular
• History of cardiovascular conditions that may interfere with the conduct or interpretation of the study or may constitute a safety risk per the investigator
• Systolic blood pressure (SBP) > 160 mmHg or diastolic blood pressure (DBP) > 90 mmHg (determined by the mean of 3 consecutive
measurements at least 5 minutes apart during screening)
• Within the 3 months prior to or during screening
a. Unstable angina or acute coronary syndrome
b. Transient ischemic attack (TIA) or stroke
c. Revascularization procedure
d. Instability in ST-segment depression between screening ETTs, as assessed by the core ECG laboratory.
• ECG findings that preclude analysis of the ETT, including but not limited to:
a. Left bundle branch block
b. Pacemaker
c. Resting ST-segment depression ≥ 1.0 mm
d. Left ventricular hypertrophy with repolarization changes
e. Wolf-Parkinson White
• Digitalis or Implantable defibrillator use |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in TET |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The ETT will be conducted in visits 2, 3 and 4 during the screening period, and after randomization and administration of study drug on Day 1. |
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E.5.2 | Secondary end point(s) |
• During the ETT
o Time to onset of exercise-induced angina
o Time to onset of ≥ 1 mm ST-segment depression
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The ETT will be conducted in visits 2, 3 and 4 during the screening period, and after randomization and administration of study drug on Day 1. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 21 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Bulgaria |
Czech Republic |
Finland |
Germany |
Latvia |
New Zealand |
Poland |
Romania |
Slovakia |
South Africa |
Switzerland |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 5 |