E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Gastraesdophageal Reflux Disease |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10018203 |
E.1.2 | Term | GERD |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal 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 |
The primary objective is to assess the pharmacokinetics of esomeprazole and its effect on intragastric pH in preterm infants and neonates. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives were:
• to assess the effect of esomeprazole on esophageal acid exposure secondary to gastroesophageal reflux (GER) using 24 hour pH monitoring and intraluminal impedance measurements
• to assess the safety and tolerability of esomeprazole in preterm infants and neonates
• to assess the ability of esomeprazole to reduce symptoms suggestive of gastroesophageal reflux disease (GERD) in preterm infants and neonates
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
For inclusion in the study patients must fulfil all of the following criteria:
1. provision of signed informed consent by parent or guardian
2. Gestational age ≥ 32 weeks and < 1 month post-term (term=38 gestational weeks)
3. Symptoms of GERD as judged by the investigator
4. Considered for treatment with an acid inhibiting agent based on symptoms of GERD as judged by the investigator
5. GERD diagnosis confirmed by 24-hour pH-monitoring, the criteria being:
reflux index (% time pH < 4) of ≥ 5%
6. Body weight ≥ 1.8 kg - ≤ 6.5 kg
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E.4 | Principal exclusion criteria |
Exclusion criteria
Any of the following is regarded as a criterion for exclusion from the study:
1. Current or historical clinically significant illness or abnormal screening laboratory values that would, as judged by the investigator, be expected to interfere with the study procedures or with the absorption, distribution, or elimination of esomeprazole, or jeopardise the safety of the patient
2. History of resectional surgery of the esophagus, stomach, duodenum or jejunum
3. Receipt of experimental drug or use of experimental device within 4 weeks preceding screening
4. Use of any pharmacological antireflux therapy within 72 hours prior to the diagnostic baseline pH impedance monitoring. Antacids (eg Mylanta) or food thickeners can be used in the 72 hour period up to one hour prior to the pH impedance monitoring
5. Need for continuous concurrent therapy with anticholinergics, antineoplastic agents, H2-receptor antagonists, sucrulfate, bismuth-containing compounds, pro-motility drugs, macrolide antibiotics or barbiturates
6. Known or suspected hypersensitivity to esomeprazole, substituted benzimidazoles or any other constituents of the formulation (glycerol monostearate 40-55, hydroxypropylcellulose, hypromellose, magnesium stearate, methacrylic acid - ethyl acrylate copolymer (1:1) dispersion 30 per cent, polysorbate 80, sugar spheres, talc, triethyl citrate)
7. Congenital drug addiction
8. Proven/suspected to be infected by Hepatitis B/C or HIV
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E.5 End points |
E.5.1 | Primary end point(s) |
· Area under the plasma concentration versus time curve within a dosing interval at steady-state (AUCĪ, in the protocol referred to as AUC, ie, area under the plasma concentration versus time curve) (primary variable)
· Apparent clearance, ie, oral clearance (CL/F)·
Apparent volume of distribution, ie oral volume of distribution (V/F)· Plasma elimination half-life (t½)
· Maximum plasma concentration at steady state (Css,max, in the protocol referred to as Cmax, ie, the maximum plasma concentration) was evaluated
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
All PK variables were assessed on Day7/8
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E.5.2 | Secondary end point(s) |
Intragastric pH measurement
• The percentage of time with intragastric pH>4 during the 24-hour period (primary variable)
Safety
Adverse events, laboratory variables, blood pressure, pulse, respiratory rate, head circumference, weight and length
Efficacy
Frequency of GERD symptoms from symptom assessment charts.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Symptom assessment during the 7 days treatment period and day 7/8.
PH measurements day 7/8
Safety during the treatment period and as a 14 days follow-up. |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | No |
E.8.1.1 | Randomised | Yes |
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 | 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 | No |
E.8.2.3 | Other | No |
E.8.3 |
Will this trial be conducted at a single site globally?
| Yes |
E.8.4 | Will this trial be conducted at multiple sites globally? | No |
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 years | 2 |