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 |
Cystic fibrosis, disorder of the lungs |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10011762 |
E.1.2 | Term | Cystic fibrosis |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic 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 assess the pharmacokinetics of doripenem after a single 30 mg/kg doripenem 4-hour i.v. infusion administered to pediatric subjects 6 to 17 years of age, inclusive, with cystic fibrosis (CF). Safety and tolerability will also be assessed. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Boy or girl between 6 years of age and 17 years of age, inclusive, with a confirmed diagnosis of CF (documented sweat chloride ≥60 mEq/L by quantitative pilocarpine iontophoresis test [QPIT] and/or homozygosity for ΔF508 genetic mutation (or heterozygosity for 2 known mutations)
- Subjects must be medically stable, without acute decline in physical condition in the investigator's judgment.
- A parent or the subject's legally acceptable representative must have signed an informed consent document indicating they understand the purpose of and procedures required for the study and are willing to participate in the study. Assent is also required of children capable of understanding the nature of the study (typically 7 years of age and older) and capable of providing it, as described in Section 11.2.3, Informed Consent/Assent and as approved by institutional-specific guidelines
- Suspected or diagnosed with an infection, colonization, or prophylaxis for which the subject is receiving antibiotic therapy
- Menarchal girls must be surgically sterile, abstinent, or, if sexually active, be practicing an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, contraceptive patch, male partner sterilization, or abstinence for the duration of the study) before entry and throughout the study
- Menarchal girls, must have a negative urine pregnancy test at screening
- If a boy, must agree to use an adequate contraception method as deemed appropriate by the investigator (e.g., abstinence, vasectomy, double-barrier, partner using effective contraception)
- Be a non-smoker |
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E.4 | Principal exclusion criteria |
- History of colonization with B. cepacia within the past 6 months
- Clinically significant abnormal values for hematology, clinical chemistry or urinalysis at screening as deemed appropriate by the investigator. If the results of the chemistry, hematology, or urinalysis tests are outside normal reference ranges for a subject’s age, even if considered to be clinically significant, the subject can be included if, in the investigator's judgment, the abnormalities are consistent with the subject's underlying disease(s) or therapies. (Goss 2006) This determination must be recorded in the subject’s source documents and initialed by the investigator
- Clinically significant abnormal physical examination or vital signs at screening as deemed appropriate by the investigator. If the results of the physical examination or vital signs, are outside normal reference ranges for a subject’s age, even if considered to be clinically significant, the subject can be included if, in the investigator's judgment, the abnormalities are consistent with the subject's underlying disease(s) or therapies. (Goss 2006) This determination must be recorded in the subject’s source documents and initialed by the investigator
- History of clinically significant allergies to medications, especially known hypersensitivity or intolerance to carbapenems, penicillins, or other β-lactam antibiotics
- Known allergy to heparin or history of heparin induced thrombocytopenia, if an indwelling cannula (e.g., heparin lock) or central line is used
- Subjects concomitantly treated with or having received imipenem/cilastin within 48 hours before study drug administration
- Subjects concomitantly treated with probenecid or VPA (refer to Section 5.5, Concomitant Therapy)
- Had substantial loss of blood (more than 10% of total blood volume) within 3 months before the administration of study drug
- Received an experimental drug or used an experimental medical device within 1 month or within a period less than 10 times the drug’s half-life, whichever is longer, before the administration of the study drug is scheduled
- If a menarchal girl, pregnant, breast-feeding or planning to become pregnant during the study
- Preplanned surgery or procedures that would interfere with the conduct of the study
- Employee of the investigator or study center, with direct involvement in the proposed study or other studies under the direction of that investigator or study center, as well as family members of the employees or the investigator.
- History of smoking or use of nicotine-containing substances within the previous 2 months, as determined by medical history or subject’s verbal report |
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E.5 End points |
E.5.1 | Primary end point(s) |
Assess the pharmacokinetics, safety and tolerability of a single 30mg/kg dose of doripenem in pediatric subjects 6 to 17 years of age, with Cystic Fibrosis. |
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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) |
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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 | 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 | Yes |
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) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Evaluate pharmacokinetics |
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E.7.2 | Therapeutic exploratory (Phase II) | No |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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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.8.9.2 | In all countries concerned by the trial months | 10 |