E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Early detection of Colorectal neoplasms |
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E.1.1.1 | Medical condition in easily understood language |
Early detection of colon cancer |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10010023 |
E.1.2 | Term | Colorectal neoplasms malignant |
E.1.2 | System Organ Class | 100000004864 |
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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 diagnostic performance (sensitivity, specificity, positive and negative predictive values, likelihood ratios, area under the curve) of 2 immunochemical Fecal Occult Blood Tests (iFOBTs) for detecting advanced colorectal neoplasms after a single dose of acetylsalicylic acid as compared to placebo |
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E.2.2 | Secondary objectives of the trial |
To study gender-specific performance of the 2 iFOBTs and the possible gain in diagnostic performance by stool sampling on multiple days.
To study the safety of single-dose acetylsalicylic acid in the selected population.
To collect blood samples for additional biomarker analyses (optional)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Age 40 to 80 years (both males and females; premenopausal women must have a negative pregnancy test before inclusion into the study, postmenopausal women are women who have not had menstrual bleeding for at least 12 months, or have been surgically sterilized)
•Planned screening or diagnostic colonoscopy
•Able to speak and understand German sufficiently to be able to give written informed consent and comply with the study requirements
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E.4 | Principal exclusion criteria |
Factors potentially influencing the primary endpoint
Diseases/symptoms:
-Chronic inflammatory bowel disease (e.g. Crohn’s disease, colitis ulcerosa)
-Colonoscopy due to positive fecal occult blood test
-History of Colorectal cancer
-Angiodysplasia of the colon
-Anamnestic or observed blood loss per anum
Use of any of the following drugs Within 2 weeks before the study:
-Anticoagulants (including, but not limited to heparin, vitamin K antagonists [e.g. phenprocoumon, warfarin], direct thrombin inhibitors [e.g. dabigatran], or factor Xa inhibitors [apixapan, rivaroxaban])
-Antiplatelet drugs (e.g. clopidogrel, prasugrel, ticlopidin)
Within 1 week before the study
-Acetylsalicylic acid Within 3 days before the study
-NSAIDs and COX-2 inhibitors
-Factors potentially affecting the safety
-Any current clinically relevant signs and symptoms, including
-Signs and symptoms suggesting acute gastrointestinal ulcer
-Known clinically relevant thrombocytopenia
.Acute infection
-Volume deficit (exsiccosis)
-Any currently present allergy with dermal reactions, pruritus, or urticaria
-Severe or insufficiently controlled asthma
-Severe kidney or liver diseases (e.g. GFR <30 ml/min, liver cirrhosis)
-Severe, not sufficiently treated heart failure (as judged by the investigator)
-Severe, poorly controlled arterial hypertension
-Any other unclear symptoms needing further investigation in the opinion of the investigator
Any of the following anamnestic findings
-History of severe gastrointestinal bleeding
-Known hemorrhagic diathesis, including, but not limited to, hypoprothrombinaemia, severe thrombocytopenia, hemophilia
-Asthma, except for patients who have used acetylsalicylic acid in the past without negative effects
-Hypersensitivity against salicylic acid or other ingredients of the study drugs
-Previous intolerance to NSAIDs, COX-2 inhibitors, or antirheumatic medication
-Severe gout (e.g. recurrent attacks)
-Hereditary oxaluria
-Known G6PD or glutathione peroxidase deficiency
-Known epilepsy with generalised seizures
-Severe cardiac diseases (including, but not limited to, myocardial infarction in the past 6 months)
Intention to use any of the following drugs during the study:
-Anticoagulants
-Antiplatelet drugs
-NSAIDs, COX-2 inhibitors
-Methotrexate ≥ 15 mg/week
-Systemic glucocorticoids
-Selective serotonin reuptake inhibitors (SSRIs)
-valproic acid
Planned surgery/dental treatment during participation in the study
Other factors
Known or suspected relevant alcohol abuse
Known or suspected illicit drug abuse
Pregnancy
Suspected non-compliance with the study procedures
Participation in another clinical study
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E.5 End points |
E.5.1 | Primary end point(s) |
Sensitivity at predefined cutpoints of test positivity of the RIDASCREEN® test to detect advanced neoplasms. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• positive and negative predictive values
• specificity and the area under the curve in ROC analyses
• likelihood ratios
• gender-specific performance of the tests
• gain in diagnostic performance by test application on multiple days
• serious adverse events
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | 17 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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 | 5 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |