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This phase IIa study is designed as a multi-centre, multinational, randomised, double-blind, placebo controlled study in three parallel groups, with the aim to evaluate the efficacy and safety of Nepadutant given at two oral doses once daily for seven days in comparison to placebo in the treatment of infantile colic.
Infant colic is a functional gastrointestinal disorders which affects up to the 30% of the infant population; it is primarily characterised by excessive inconsolable crying starting without any apparent cause and lasting for several hours per day.
Current non pharmacological interventions (e.g. message, restriction in maternal diet in breast-feeding infants) and pharmacological treatments (simethicone, antimuscarinic drugs) are largely unsatisfactory.
In animal models, Nepadutant reverse the exaggerated intestinal motility and sensitivity, induced by different stimuli, without producing inhibitory effects on these functions at baseline, suggesting that Nepadutant could have a therapeutic effect with no interference on physiological gastrointestinal transit.
This phase IIa study is designed to evaluate the efficacy of Nepadutant paediatric oral solution given once daily at two doses in comparison to placebo.
The experimental clinical phase encompasses the following periods:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Nepadutant Low Dose | Experimental |
| |
| Nepadutant High Dose | Experimental |
| |
| Placebo | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Nepadutant oral solution | Drug | Oral administration once daily for 7 days |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Absolute Change of the Mean Daily Crying and Fussing Time for Three Consecutive Days While on Treatment Versus Baseline. | Efficacy assessment to be measured through "baby's day" diary recorded for three consecutive days while on treatment (i.e. starting from 6 pm on Day 4 and continued for 72 hours) vs baseline (i.e. starting from 6 pm on Day -4 until 1st treatment administration). | Baseline and one week |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of 'Responder' Babies at the End of Treatment Period. | Response is defined as a decrease of at least 50% of crying and fussing time during the last 3 days on treatment vs baseline. | baseline and one week |
| Absolute Change in the Overall Parental Judgment After the First Dose of Treatment Versus Baseline |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Sibylle Koletzko, MD | Dr. v. Haunersches Kinderspital Ludwig Maximilians University D- 80337 München, Germany | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Dr. von Haunersches Kinderspital Ludwig Maximilians Universität München | München | 80337 | Germany | |||
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| ID | Title | Description |
|---|---|---|
| FG000 | Nepadutant Low Dose | Nepadutant oral solution 0.1mg/kg: Oral administration once daily for 7 days |
| FG001 | Nepadutant High Dose | Nepadutant oral solution 0.5mg/kg: Oral administration once daily for 7 days |
| FG002 | Placebo | Placebo matching Nepadutant oral solution: Oral administration once daily for 7 days |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
113 : ITT - defined as the safety population randomised with at least 24h diary recording post 1st dose of study treatment
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| ID | Title | Description |
|---|---|---|
| BG000 | Nepadutant Low Dose | Nepadutant oral solution: Oral administration once daily for 7 days |
| BG001 | Nepadutant High Dose | Nepadutant oral solution: Oral administration once daily for 7 days |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Absolute Change of the Mean Daily Crying and Fussing Time for Three Consecutive Days While on Treatment Versus Baseline. | Efficacy assessment to be measured through "baby's day" diary recorded for three consecutive days while on treatment (i.e. starting from 6 pm on Day 4 and continued for 72 hours) vs baseline (i.e. starting from 6 pm on Day -4 until 1st treatment administration). | 112 instead of 113, because 1 subject had no records at baseline and therefore the outcome could not be measured | Posted | Mean | Standard Deviation | Minutes | Baseline and one week |
|
4 weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Nepadutant Low Dose | Nepadutant oral solution: Oral administration once daily for 7 days |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Bronchitis | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Hospitalization for Bronchitis in a 10 weeks-old male infant. The investigator considered the SAE as unlikely related to the study drug. It resolved without sequel. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (Unspecified) |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Angela Capriati | Menarini Ricerche | +39 05556809990 | acapriati@menarini-ricerche.it |
| ID | Term |
|---|---|
| D003085 | Colic |
| ID | Term |
|---|---|
| D007232 | Infant, Newborn, Diseases |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
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| ID | Term |
|---|---|
| C107754 | MEN 11420 |
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| Nepadutant oral solution |
| Drug |
Oral administration once daily for 7 days |
|
| Placebo matching Nepadutant oral solution | Drug | Oral administration once daily for 7 days |
|
On a daily basis parents expressed an overall judgement on the study treatment effect based on a 6 rate categorical scale from 0 to 5 (where 0 is for "Not at all" and 5 is "Extremely". The question was "How frustrating to you was your baby's crying today?") |
| 1 day |
| Absolute Change in the Overall Parental Judgment at the End of Treatment Versus Baseline | On a daily basis parents expressed an overall judgement on the study treatment effect based on a 6 rate categorical scale from 0 to 5 (where 0 is for "Not at all" and 5 is "Extremely". The question was "How frustrating to you was your baby's crying today?") | 1 week |
| Absolute Change in the Overall Parental Judgment After Treatment Discontinuation Versus Baseline | On a daily basis parents expressed an overall judgement on the study treatment effect based on a 6 rate categorical scale from 0 to 5 (where 0 is for "Not at all" and 5 is "Extremely". The question was "How frustrating to you was your baby's crying today?") | 10 days |
| Safety and Tolerability Will be Assessed in Terms of Frequency and Severity of AEs as Well as Frequency of Clinically Significant Changes in Physical Examination and Lab Test. | Safety and tolerability will be assessed for the Safety Population (all patients who received the study drug) in terms of frequency and severity of AEs as well as frequency of clinically significant changes in physical examination and lab test. | up to four weeks |
| Klinika Patologii Noworodkow, Niemowlat I Kardiologii, Dzieciecy Szpital Kliniczny |
| Lublin |
| 20-093 |
| Poland |
| Federal Scientific Clinical Center of Children Hematology, Oncology and Immunology | Moscow | 117997 | Russia |
| Moscow State Healthcare Institution Municipal Pediatric health center â„– 10 | Moscow | 119331 | Russia |
| Moscow State Medical University | Moscow | 119991 | Russia |
| Federal Scientific Clinical Center of Children Hematology, Oncology and Immunology | Moscow | 123317 | Russia |
| St. Petersburg State Pediatric Medical Academy | Saint Petersburg | 194100 | Russia |
| St. Petersburg State Institution of Healthcare Municipal Pediatric health center â„– 35 | Saint Petersburg | 199191 | Russia |
| Pediatrics Department of Clinical sciences Umeå university | Umeå | SE-901 85 | Sweden |
| BG002 | Placebo | Placebo matching Nepadutant oral solution: Oral administration once daily for 7 days |
| BG003 | Total | Total of all reporting groups |
| weeks |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Weight | Mean | Standard Deviation | kg |
|
| Feeding Mode | Feeding mode: 1 data missing in high dose - 0.5mg/kg (37 subjects instead of 38) | Number | participants |
|
Nepadutant oral solution: Oral administration once daily for 7 days |
| OG002 | Placebo | Placebo matching Nepadutant oral solution: Oral administration once daily for 7 days |
|
|
| Secondary | Percentage of 'Responder' Babies at the End of Treatment Period. | Response is defined as a decrease of at least 50% of crying and fussing time during the last 3 days on treatment vs baseline. | 112 instead of 113, because 1 subject had no records at baseline and therefore the outcome could not be measured | Posted | Number | Responders Rate (% of responders babies) | baseline and one week |
|
|
|
| Secondary | Absolute Change in the Overall Parental Judgment After the First Dose of Treatment Versus Baseline | On a daily basis parents expressed an overall judgement on the study treatment effect based on a 6 rate categorical scale from 0 to 5 (where 0 is for "Not at all" and 5 is "Extremely". The question was "How frustrating to you was your baby's crying today?") | ITT - defined as the safety population randomised with at least 24h diary recording post 1st dose of study treatment | Posted | Mean | Standard Deviation | Score range 0-5 | 1 day | Questionnaires completed by parents | Participants |
|
|
|
| Secondary | Absolute Change in the Overall Parental Judgment at the End of Treatment Versus Baseline | On a daily basis parents expressed an overall judgement on the study treatment effect based on a 6 rate categorical scale from 0 to 5 (where 0 is for "Not at all" and 5 is "Extremely". The question was "How frustrating to you was your baby's crying today?") | ITT - defined as the safety population randomised with at least 24h diary recording post 1st dose of study treatment | Posted | Mean | Standard Deviation | Score range 0-5 | 1 week | Questionnaires completed by parents | Participants |
|
|
|
| Secondary | Absolute Change in the Overall Parental Judgment After Treatment Discontinuation Versus Baseline | On a daily basis parents expressed an overall judgement on the study treatment effect based on a 6 rate categorical scale from 0 to 5 (where 0 is for "Not at all" and 5 is "Extremely". The question was "How frustrating to you was your baby's crying today?") | ITT - defined as the safety population randomised with at least 24h diary recording post 1st dose of study treatment | Posted | Mean | Standard Deviation | Score range 0-5 | 10 days | Questionnaires completed by parents | Participants |
|
|
|
| Secondary | Safety and Tolerability Will be Assessed in Terms of Frequency and Severity of AEs as Well as Frequency of Clinically Significant Changes in Physical Examination and Lab Test. | Safety and tolerability will be assessed for the Safety Population (all patients who received the study drug) in terms of frequency and severity of AEs as well as frequency of clinically significant changes in physical examination and lab test. | All patients receiving the study drug (114) | Posted | Number | Adverse events | up to four weeks |
|
|
|
| 0 |
| 40 |
| 9 |
| 40 |
| EG001 | Nepadutant High Dose | Nepadutant oral solution: Oral administration once daily for 7 days | 1 | 38 | 6 | 38 |
| EG002 | Placebo | Placebo matching Nepadutant oral solution: Oral administration once daily for 7 days | 0 | 36 | 5 | 36 |
|
| Aphthous stomatitis | Gastrointestinal disorders | MedDRA (Unspecified) |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (Unspecified) |
|
| Frequent bowel movements | Gastrointestinal disorders | MedDRA (Unspecified) |
|
| Infrequent bowel movements | Gastrointestinal disorders | MedDRA (Unspecified) |
|
| Salivary ipersecretion | Gastrointestinal disorders | MedDRA (Unspecified) |
|
| Vomiting | Gastrointestinal disorders | MedDRA (Unspecified) |
|
| Pyrexia | General disorders | MedDRA (Unspecified) |
|
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA (Unspecified) |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (Unspecified) |
|
| Viral infection | Infections and infestations | MedDRA (Unspecified) |
|
| Body temperature increased | Investigations | MedDRA (Unspecified) |
|
| Gamma -GT abnormal | Investigations | MedDRA (Unspecified) |
|
| Crying | Nervous system disorders | MedDRA (Unspecified) |
|
| Apnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (Unspecified) |
|
| Skin lesion | Skin and subcutaneous tissue disorders | MedDRA (Unspecified) |
|
| Regurgitation | Gastrointestinal disorders | MedDRA (Unspecified) |
|
The results of the study cannot be submitted for presentation, abstract, poster exhibition, or publication by the investigator until Menarini Ricerche S.p.A. has reviewed/commented and agreed to any publication.