Infantile Colic
Conditions
Keywords
Infantile Colic, tachykinin antagonist, Nepadutant
Brief summary
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.
Detailed description
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: * Screening period (no study medication) to be done 7 to 4 days prior to randomisation * Treatment period, lasting seven days with once daily administration * Post treatment period, lasting seven days A safety follow-up visit will be performed approximately 1 month after the first administered dose.
Interventions
Oral administration once daily for 7 days
Oral administration once daily for 7 days
Sponsors
Menarini Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
4 Weeks to 20 Weeks
Healthy volunteers
No
Inclusion criteria
* Healthy infants with diagnosis of infant colic according to the following modified Wessel criterion paroxysm of irritability, fussing or crying that start and stop without obvious cause for \>3h/day, \>3 days/week for one week * Age \> 4 weeks and \< 20 weeks * Infants breast-fed mixed fed or formula fed with a stable dietary regimen * Normal growth * History of no adequate response to conventional treatment alternatives which make the infants in need of medical treatment * Willingness to refrain from use of antimuscarinic drugs, simethicone, dimethicone or antiacids during the study period.
Exclusion criteria
* Clinical evidence of allergies or other diseases which may cause crying and/or fussiness or may interfere with absorption or clearance of the drug. * Suspect of gastroesophageal reflux disease (GERD) * Suspect of cow milk allergy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change of the Mean Daily Crying and Fussing Time for Three Consecutive Days While on Treatment Versus Baseline. | Baseline and one week | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of 'Responder' Babies at the End of Treatment Period. | baseline and one week | Response is defined as a decrease of at least 50% of crying and fussing time during the last 3 days on treatment vs baseline. |
| Absolute Change in the Overall Parental Judgment After the First Dose of Treatment Versus Baseline | 1 day | 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?) |
| Absolute Change in the Overall Parental Judgment at the End of Treatment Versus Baseline | 1 week | 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?) |
| Absolute Change in the Overall Parental Judgment After Treatment Discontinuation Versus Baseline | 10 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?) |
| 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. | up to four weeks | 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. |
Countries
Germany, Poland, Russia, Sweden
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Nepadutant Low Dose Nepadutant oral solution: Oral administration once daily for 7 days | 39 |
| Nepadutant High Dose Nepadutant oral solution: Oral administration once daily for 7 days | 38 |
| Placebo Placebo matching Nepadutant oral solution: Oral administration once daily for 7 days | 36 |
| Total | 113 |
Baseline characteristics
| Characteristic | Total | Nepadutant Low Dose | Placebo | Nepadutant High Dose |
|---|---|---|---|---|
| Age, Continuous | 11.1 weeks STANDARD_DEVIATION 4.881 | 11.03 weeks STANDARD_DEVIATION 4.909 | 10.92 weeks STANDARD_DEVIATION 4.686 | 11.34 weeks STANDARD_DEVIATION 5.147 |
| Feeding Mode Breast Fed | 85 participants | 27 participants | 29 participants | 29 participants |
| Feeding Mode Formula Fed | 23 participants | 9 participants | 7 participants | 7 participants |
| Feeding Mode Mixed Fed | 4 participants | 3 participants | 0 participants | 1 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 111 Participants | 38 Participants | 36 Participants | 37 Participants |
| Sex: Female, Male Female | 51 Participants | 21 Participants | 17 Participants | 13 Participants |
| Sex: Female, Male Male | 62 Participants | 18 Participants | 19 Participants | 25 Participants |
| Weight | 5.35 kg STANDARD_DEVIATION 1.275 | 5.22 kg STANDARD_DEVIATION 1.129 | 5.61 kg STANDARD_DEVIATION 1.419 | 5.24 kg STANDARD_DEVIATION 1.267 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 9 / 40 | 6 / 38 | 5 / 36 |
| serious Total, serious adverse events | 0 / 40 | 1 / 38 | 0 / 36 |
Outcome results
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).
Time frame: Baseline and one week
Population: 112 instead of 113, because 1 subject had no records at baseline and therefore the outcome could not be measured
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nepadutant Low Dose | Absolute Change of the Mean Daily Crying and Fussing Time for Three Consecutive Days While on Treatment Versus Baseline. | End of Treatment | 185.8 Minutes | Standard Deviation 100.97 |
| Nepadutant Low Dose | Absolute Change of the Mean Daily Crying and Fussing Time for Three Consecutive Days While on Treatment Versus Baseline. | Baseline | 284.57 Minutes | Standard Deviation 89.298 |
| Nepadutant Low Dose | Absolute Change of the Mean Daily Crying and Fussing Time for Three Consecutive Days While on Treatment Versus Baseline. | Change | -96.9 Minutes | Standard Deviation 74.12 |
| Nepadutant High Dose | Absolute Change of the Mean Daily Crying and Fussing Time for Three Consecutive Days While on Treatment Versus Baseline. | End of Treatment | 154.4 Minutes | Standard Deviation 102 |
| Nepadutant High Dose | Absolute Change of the Mean Daily Crying and Fussing Time for Three Consecutive Days While on Treatment Versus Baseline. | Baseline | 273.6 Minutes | Standard Deviation 86.356 |
| Nepadutant High Dose | Absolute Change of the Mean Daily Crying and Fussing Time for Three Consecutive Days While on Treatment Versus Baseline. | Change | -119.2 Minutes | Standard Deviation 97.13 |
| Placebo | Absolute Change of the Mean Daily Crying and Fussing Time for Three Consecutive Days While on Treatment Versus Baseline. | Baseline | 283.91 Minutes | Standard Deviation 80.201 |
| Placebo | Absolute Change of the Mean Daily Crying and Fussing Time for Three Consecutive Days While on Treatment Versus Baseline. | Change | -91.2 Minutes | Standard Deviation 76.2 |
| Placebo | Absolute Change of the Mean Daily Crying and Fussing Time for Three Consecutive Days While on Treatment Versus Baseline. | End of Treatment | 192.7 Minutes | Standard Deviation 85.41 |
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?)
Time frame: 1 day
Population: ITT - defined as the safety population randomised with at least 24h diary recording post 1st dose of study treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nepadutant Low Dose | Absolute Change in the Overall Parental Judgment After the First Dose of Treatment Versus Baseline | -0.38 Score range 0-5 | Standard Deviation 0.771 |
| Nepadutant High Dose | Absolute Change in the Overall Parental Judgment After the First Dose of Treatment Versus Baseline | -0.68 Score range 0-5 | Standard Deviation 0.884 |
| Placebo | Absolute Change in the Overall Parental Judgment After the First Dose of Treatment Versus Baseline | -0.34 Score range 0-5 | Standard Deviation 0.596 |
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?)
Time frame: 10 days
Population: ITT - defined as the safety population randomised with at least 24h diary recording post 1st dose of study treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nepadutant Low Dose | Absolute Change in the Overall Parental Judgment After Treatment Discontinuation Versus Baseline | -1.35 Score range 0-5 | Standard Deviation 0.857 |
| Nepadutant High Dose | Absolute Change in the Overall Parental Judgment After Treatment Discontinuation Versus Baseline | -1.78 Score range 0-5 | Standard Deviation 1.176 |
| Placebo | Absolute Change in the Overall Parental Judgment After Treatment Discontinuation Versus Baseline | -1.39 Score range 0-5 | Standard Deviation 0.896 |
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?)
Time frame: 1 week
Population: ITT - defined as the safety population randomised with at least 24h diary recording post 1st dose of study treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nepadutant Low Dose | Absolute Change in the Overall Parental Judgment at the End of Treatment Versus Baseline | -1.24 Score range 0-5 | Standard Deviation 0.909 |
| Nepadutant High Dose | Absolute Change in the Overall Parental Judgment at the End of Treatment Versus Baseline | -1.75 Score range 0-5 | Standard Deviation 1.186 |
| Placebo | Absolute Change in the Overall Parental Judgment at the End of Treatment Versus Baseline | -1.23 Score range 0-5 | Standard Deviation 1.044 |
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.
Time frame: baseline and one week
Population: 112 instead of 113, because 1 subject had no records at baseline and therefore the outcome could not be measured
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nepadutant Low Dose | Percentage of 'Responder' Babies at the End of Treatment Period. | 36.8 Responders Rate (% of responders babies) |
| Nepadutant High Dose | Percentage of 'Responder' Babies at the End of Treatment Period. | 55.3 Responders Rate (% of responders babies) |
| Placebo | Percentage of 'Responder' Babies at the End of Treatment Period. | 19.4 Responders Rate (% of responders babies) |
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.
Time frame: up to four weeks
Population: All patients receiving the study drug (114)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nepadutant Low Dose | 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. | 9 Adverse events |
| Nepadutant High Dose | 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. | 6 Adverse events |
| Placebo | 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. | 5 Adverse events |