Colic
Conditions
Keywords
Feeding intolerance, Infant, tachykinin antagonist, Infant colic, Nepadutant
Brief summary
The present pilot study is aimed to obtain preliminary data on the effect of three ascending oral dose levels of nepadutant on the relief of symptoms associated with feeding intolerance. In addition, the assessment of drug exposure (PK assessment) will provide additional information on the dose-effect relationship, thus supporting the dose selection and dosing schedule in the future studies.
Detailed description
Feeding intolerance is a transient neuro-developmental phenomenon affecting 25% to 40% of infant and toddler, with a peak at 6 weeks of age. Feeding problems include mainly vomiting, slow feeding, refusal to eat and colic. Current non pharmacological interventions (e.g. message, restriction in maternal diet in breast-feeding infants) and pharmacological treatments (simethicone, antimuscarinic drugs and antiacids) are largely unsatisfactory. Nepadutant is postulated to have a therapeutic effect in infant colic since it reverts exaggerated intestinal motility and sensitivity induced by different stimuli through the activation of neurokinin-2 receptors, without interferring on the on physiological gastrointestinal transit. This phase IIa study is designed to test in each participant infant two out of three oral doses of nepadutant in order to measure its blood levels, safety and efficacy with each dose level to be given for 7 concecutive days. The experimental clinical phase encompasses the following periods: * Screening period (no study medication), lasting approximately 7 days prior to randomization * Treatment period, lasting fourteen days (7 days fore each dose)with once daily administration * A safety follow-up visit, approximately four weeks after start of treatment.
Interventions
DRUGNepadutant
Nepadutant oral solution
Sponsors
Menarini Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 6 Months
Healthy volunteers
No
Inclusion criteria
* Infants with a clinical diagnosis of feeding intolerance. * Age ≤ 6 months at the enrolment. * Normal growth. * Infants who can refrain from use of erythromycin, metoclopramide, antihistaminic drug, proton pump inhibitors (PPIs), antacids, antimuscarinic drugs, simethicone and dimethicone from 1 week prior randomization until end of study.
Exclusion criteria
* Any clinically relevant event (excluding those relevant to the condition under study) which has occurred within one week prior to randomization. * Any pharmacological treatment starting within one week prior to randomization. * Infants for whom a change in the diet (i.e. weaning) has been performed within one week prior to randomization or is planned during the study period.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Absolute Differences of I-GERQ-R Total Score at V4 (End of 2nd Week of Treatment) Respect to V3 (End of 1st Week of Treatment). | V3 (end of 1st week of treatment) and V4 (end of 2nd week of treatment) | The results obtained at V3 are used as baseline for the second week treatment period (V4). Infant Gastroesophageal Reflux Questionnaire Revised (I-GERQ-R ), with a minimum-maximum score of 0-42 (minimum for diagnosis \>15). The higher values reflect worse outcome. The questionnaire comprised 12 items as questions quantifying aspects of regurgitation (3 questions), crying (3 questions), feeding refusal (2 questions), apnea/cyanosis (2 questions), hiccups and arching. Questions with 4 possible options have a score ranging from 0 to 3; questions with 5 possible options have a score ranging from 0 to 4. The scores of each item are summed, so the total score is presented. |
| I-GERQ-R Score Changes vs Baseline (Visit 2) by First Dose Level (0.1mg/kg and 0.5mg/kg). | Baseline (V2) and end of 1st week of treatment(V3) | Change in Infant Gastroesophageal Reflux Questionnaire Revised (I-GERQ-R) Score. Assessing the I-GERQ-R score changes vs baseline (Visit 2) by first dose level (0.1mg/kg and 0.5mg/kg). Infant Gastroesophageal Reflux Questionnaire Revised (I-GERQ-R ), with a minimum-maximum score of 0-42 (minimum for diagnosis \>15). The higher values reflect worse outcome. The questionnaire comprised 12 items as questions quantifying aspects of regurgitation (3 questions), crying (3 questions), feeding refusal (2 questions), apnea/cyanosis (2 questions), hiccups and arching. Questions with 4 possible options have a score ranging from 0 to 3; questions with 5 possible options have a score ranging from 0 to 4. The scores of each item are summed, so the total score is presented. |
| I-GERQ-R Score Changes vs Visit 3 by Second Dose Level (0.5mg/kg and 1mg/kg). | end of first week of treatment (V3) and end of second week of treatment (V4) | Change in Infant Gastroesophageal Reflux Questionnaire Revised (I-GERQ-R) Score. Assessing the I-GERQ-R score changes vs Visit 3 by second dose level (0.5mg/kg and 1mg/kg). Infant Gastroesophageal Reflux Questionnaire Revised (I-GERQ-R ), with a minimum-maximum score of 0-42 (minimum for diagnosis \>15). The higher values reflect worse outcome. The questionnaire comprised 12 items as questions quantifying aspects of regurgitation (3 questions), crying (3 questions), feeding refusal (2 questions), apnea/cyanosis (2 questions), hiccups and arching. Questions with 4 possible options have a score ranging from 0 to 3; questions with 5 possible options have a score ranging from 0 to 4. The scores of each item are summed, so the total score is presented. |
| The Absolute Differences of I-GERQ-R Total Score at V3 (End of First Week of Treatment) Respect to the Baseline (V2). | Baseline (V2) and end of first week of treatment (V3) | Results obtained at V2 serve as baseline values for the assessment of effects at V3 (i.e. end of first week of treatment). Infant Gastroesophageal Reflux Questionnaire Revised (I-GERQ-R ), with a minimum-maximum score of 0-42 (minimum for diagnosis \>15). The higher values reflect worse outcome. The questionnaire comprised 12 items as questions quantifying aspects of regurgitation (3 questions), crying (3 questions), feeding refusal (2 questions), apnea/cyanosis (2 questions), hiccups and arching. Questions with 4 possible options have a score ranging from 0 to 3; questions with 5 possible options have a score ranging from 0 to 4. The scores of each item are summed, so the total score is presented. |
| The Absolute Differences of I-GERQ-R Total Score at V5 (Follow-up) Respect to V2 (Baseline). | Baseline (V2) and follow up 2 weeks after the last administered dose (V5) | Results obtained at V2 serve as baseline values for follow-up assessment 2 weeks after the last administered dose (V5) Infant Gastroesophageal Reflux Questionnaire Revised (I-GERQ-R ), with a minimum-maximum score of 0-42 (minimum for diagnosis \>15). The higher values reflect worse outcome. The questionnaire comprised 12 items as questions quantifying aspects of regurgitation (3 questions), crying (3 questions), feeding refusal (2 questions), apnea/cyanosis (2 questions), hiccups and arching. Questions with 4 possible options have a score ranging from 0 to 3; questions with 5 possible options have a score ranging from 0 to 4. The scores of each item are summed, so the total score is presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| A Population Pharmacokinetic Analysis to Characterize the Plasma Concentration-time Course for Nepadutant in Infant With Colics From NIC-04 | 0.5, 1, 2, 3 hours post Single Dose and 24 hours post Repeated Dose | The population pharmacokinetic analyses is presented. PopPK Clearance estimated with a one compartment model with first order absorption and elimination. |
| Incidence and Severity of AEs_ Number of Adverse Events by Treatment Dose Level | up to 4 weeks | The analysis is by treatment - Each infant was treated with two out of three ascending dose (0.1, 0.5 or 1.0 mg/kg), therefore counted in more than one dose level. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 3 Nepadutant low dose (0.1mg/kg) for 7 days followed by Nepadutant high dose (1mg/kg) for additional 7 days
Nepadutant: Nepadutant oral solution | 6 |
| Cohort 2 Nepadutant medium dose (0.5mg/kg) for 7 days followed by Nepadutant high dose (1mg/kg) for additional 7 days
Nepadutant: Nepadutant oral solution | 15 |
| Cohort 1 Nepadutant low dose (0.1mg/kg) for 7 days followed by Nepadutant medium dose (0.5mg/kg) for additional 7 days
Nepadutant: Nepadutant oral solution | 6 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Cohort 3 | Cohort 2 | Cohort 1 | Total |
|---|---|---|---|---|
| Age, Continuous | 12.52 weeks STANDARD_DEVIATION 4.281 | 13.62 weeks STANDARD_DEVIATION 6.468 | 14.27 weeks STANDARD_DEVIATION 6.559 | 13.52 weeks STANDARD_DEVIATION 5.89 |
| I-GERQ-R total score | 24.8 Score on a scale STANDARD_DEVIATION 5.4 | 19 Score on a scale STANDARD_DEVIATION 6.32 | 21.8 Score on a scale STANDARD_DEVIATION 9.91 | 20.8 Score on a scale STANDARD_DEVIATION 7.22 |
| Race/Ethnicity, Customized Black or African American | 3 particpants | 4 particpants | 1 particpants | 8 particpants |
| Race/Ethnicity, Customized More than one race | 0 particpants | 3 particpants | 0 particpants | 3 particpants |
| Race/Ethnicity, Customized White | 3 particpants | 8 particpants | 5 particpants | 16 particpants |
| Region of Enrollment United States | 6 participants | 15 participants | 6 participants | 27 participants |
| Sex: Female, Male Female | 4 Participants | 8 Participants | 2 Participants | 14 Participants |
| Sex: Female, Male Male | 2 Participants | 7 Participants | 4 Participants | 13 Participants |
| Weight | 5.323 Kg STANDARD_DEVIATION 0.9085 | 5.623 Kg STANDARD_DEVIATION 1.1045 | 5.708 Kg STANDARD_DEVIATION 1.764 | 5.576 Kg STANDARD_DEVIATION 1.1975 |
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 | 12 / 21 | 2 / 21 | 8 / 12 |
| serious Total, serious adverse events | 1 / 21 | 0 / 21 | 1 / 12 |
Outcome results
Primary
I-GERQ-R Score Changes vs Baseline (Visit 2) by First Dose Level (0.1mg/kg and 0.5mg/kg).
Change in Infant Gastroesophageal Reflux Questionnaire Revised (I-GERQ-R) Score. Assessing the I-GERQ-R score changes vs baseline (Visit 2) by first dose level (0.1mg/kg and 0.5mg/kg). Infant Gastroesophageal Reflux Questionnaire Revised (I-GERQ-R ), with a minimum-maximum score of 0-42 (minimum for diagnosis \>15). The higher values reflect worse outcome. The questionnaire comprised 12 items as questions quantifying aspects of regurgitation (3 questions), crying (3 questions), feeding refusal (2 questions), apnea/cyanosis (2 questions), hiccups and arching. Questions with 4 possible options have a score ranging from 0 to 3; questions with 5 possible options have a score ranging from 0 to 4. The scores of each item are summed, so the total score is presented.
Time frame: Baseline (V2) and end of 1st week of treatment(V3)
Population: Subjects with feeding intolerance who received at least 1 dose of nepadutant (first dose level 0.1mg/kg and 0.5 mg/kg).~One subject in the 3rd cohort didn't report I-GERQ-R score at V2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 3 | I-GERQ-R Score Changes vs Baseline (Visit 2) by First Dose Level (0.1mg/kg and 0.5mg/kg). | -6.8 score on a scale | Standard Deviation 7.31 |
| Cohort 2 | I-GERQ-R Score Changes vs Baseline (Visit 2) by First Dose Level (0.1mg/kg and 0.5mg/kg). | -7.6 score on a scale | Standard Deviation 5.5 |
Primary
I-GERQ-R Score Changes vs Visit 3 by Second Dose Level (0.5mg/kg and 1mg/kg).
Change in Infant Gastroesophageal Reflux Questionnaire Revised (I-GERQ-R) Score. Assessing the I-GERQ-R score changes vs Visit 3 by second dose level (0.5mg/kg and 1mg/kg). Infant Gastroesophageal Reflux Questionnaire Revised (I-GERQ-R ), with a minimum-maximum score of 0-42 (minimum for diagnosis \>15). The higher values reflect worse outcome. The questionnaire comprised 12 items as questions quantifying aspects of regurgitation (3 questions), crying (3 questions), feeding refusal (2 questions), apnea/cyanosis (2 questions), hiccups and arching. Questions with 4 possible options have a score ranging from 0 to 3; questions with 5 possible options have a score ranging from 0 to 4. The scores of each item are summed, so the total score is presented.
Time frame: end of first week of treatment (V3) and end of second week of treatment (V4)
Population: Subjects with feeding intolerance who received at least 1 dose of nepadutant (second dose level 0.5mg/kg and 1 mg/kg)~1 subject in the first cohort early terminated after V2
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 3 | I-GERQ-R Score Changes vs Visit 3 by Second Dose Level (0.5mg/kg and 1mg/kg). | -1.4 Score as sum of units | Standard Deviation 0.89 |
| Cohort 2 | I-GERQ-R Score Changes vs Visit 3 by Second Dose Level (0.5mg/kg and 1mg/kg). | -4.9 Score as sum of units | Standard Deviation 4.41 |
Primary
The Absolute Differences of I-GERQ-R Total Score at V3 (End of First Week of Treatment) Respect to the Baseline (V2).
Results obtained at V2 serve as baseline values for the assessment of effects at V3 (i.e. end of first week of treatment). Infant Gastroesophageal Reflux Questionnaire Revised (I-GERQ-R ), with a minimum-maximum score of 0-42 (minimum for diagnosis \>15). The higher values reflect worse outcome. The questionnaire comprised 12 items as questions quantifying aspects of regurgitation (3 questions), crying (3 questions), feeding refusal (2 questions), apnea/cyanosis (2 questions), hiccups and arching. Questions with 4 possible options have a score ranging from 0 to 3; questions with 5 possible options have a score ranging from 0 to 4. The scores of each item are summed, so the total score is presented.
Time frame: Baseline (V2) and end of first week of treatment (V3)
Population: Infants with feeding intolerance who received at least 1 dose of nepadutant. In the 3rd cohort 1 subject didn't report I-GERQ-R score at randomization. In the 1rst cohort 1 patient early terminated after V2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 3 | The Absolute Differences of I-GERQ-R Total Score at V3 (End of First Week of Treatment) Respect to the Baseline (V2). | -6.8 score on a scale | Standard Deviation 9.55 |
| Cohort 2 | The Absolute Differences of I-GERQ-R Total Score at V3 (End of First Week of Treatment) Respect to the Baseline (V2). | -7.6 score on a scale | Standard Deviation 5.5 |
| Cohort 1 | The Absolute Differences of I-GERQ-R Total Score at V3 (End of First Week of Treatment) Respect to the Baseline (V2). | -6.8 score on a scale | Standard Deviation 5.81 |
Primary
The Absolute Differences of I-GERQ-R Total Score at V4 (End of 2nd Week of Treatment) Respect to V3 (End of 1st Week of Treatment).
The results obtained at V3 are used as baseline for the second week treatment period (V4). Infant Gastroesophageal Reflux Questionnaire Revised (I-GERQ-R ), with a minimum-maximum score of 0-42 (minimum for diagnosis \>15). The higher values reflect worse outcome. The questionnaire comprised 12 items as questions quantifying aspects of regurgitation (3 questions), crying (3 questions), feeding refusal (2 questions), apnea/cyanosis (2 questions), hiccups and arching. Questions with 4 possible options have a score ranging from 0 to 3; questions with 5 possible options have a score ranging from 0 to 4. The scores of each item are summed, so the total score is presented.
Time frame: V3 (end of 1st week of treatment) and V4 (end of 2nd week of treatment)
Population: Infants with feeding intolerance who received at least 1 dose of nepadutant. In the 3rd cohort 1 subject didn't report I-GERQ-R score at randomization. In the 1rst cohort 1 patient early terminated after V2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 3 | The Absolute Differences of I-GERQ-R Total Score at V4 (End of 2nd Week of Treatment) Respect to V3 (End of 1st Week of Treatment). | -15.2 Score as sum of units | Standard Deviation 5.54 |
| Cohort 2 | The Absolute Differences of I-GERQ-R Total Score at V4 (End of 2nd Week of Treatment) Respect to V3 (End of 1st Week of Treatment). | -11.9 Score as sum of units | Standard Deviation 6.8 |
| Cohort 1 | The Absolute Differences of I-GERQ-R Total Score at V4 (End of 2nd Week of Treatment) Respect to V3 (End of 1st Week of Treatment). | -8.6 Score as sum of units | Standard Deviation 6.66 |
Primary
The Absolute Differences of I-GERQ-R Total Score at V5 (Follow-up) Respect to V2 (Baseline).
Results obtained at V2 serve as baseline values for follow-up assessment 2 weeks after the last administered dose (V5) Infant Gastroesophageal Reflux Questionnaire Revised (I-GERQ-R ), with a minimum-maximum score of 0-42 (minimum for diagnosis \>15). The higher values reflect worse outcome. The questionnaire comprised 12 items as questions quantifying aspects of regurgitation (3 questions), crying (3 questions), feeding refusal (2 questions), apnea/cyanosis (2 questions), hiccups and arching. Questions with 4 possible options have a score ranging from 0 to 3; questions with 5 possible options have a score ranging from 0 to 4. The scores of each item are summed, so the total score is presented.
Time frame: Baseline (V2) and follow up 2 weeks after the last administered dose (V5)
Population: Infants with feeding intolerance who received at least 1 dose of nepadutant. In the 3rd cohort 1 subject didn't report I-GERQ-R score at randomization. In the 1rst cohort 1 patient early terminated after V2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 3 | The Absolute Differences of I-GERQ-R Total Score at V5 (Follow-up) Respect to V2 (Baseline). | -7.8 Score as sum of units | Standard Deviation 7.6 |
| Cohort 2 | The Absolute Differences of I-GERQ-R Total Score at V5 (Follow-up) Respect to V2 (Baseline). | -11.1 Score as sum of units | Standard Deviation 6.78 |
| Cohort 1 | The Absolute Differences of I-GERQ-R Total Score at V5 (Follow-up) Respect to V2 (Baseline). | -9.8 Score as sum of units | Standard Deviation 7.4 |
Secondary
A Population Pharmacokinetic Analysis to Characterize the Plasma Concentration-time Course for Nepadutant in Infant With Colics From NIC-04
The population pharmacokinetic analyses is presented. The PopPK parameter fraction of the dose absorbed (F1) is estimated with a one compartment model with first order absorption and elimination.The results are presented fraction of the absorbed dose with 95% CI of the parameter estimate value
Time frame: 0.5, 1, 2, 3 hours post Single Dose and 24 hours post Repeated Dose
Population: At visit 2, samples from 6 subjects in Cohort 1 at 0.1mg/kg; 6 subjects in Cohort 3 at 0,1 mg/kg; 15 subjects in Cohort 2 at 0.5 mg/kg.~At visit 3\*, 4\*: samples from 5 subjects in Cohort 1 (0.1 - 0.5 mg/kg), 15 subjects in Cohort 2 (0.5 - 1 mg/kg) and 6 subjects in Cohort 3 (0.1 - 1 mg/kg).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cohort 3 | A Population Pharmacokinetic Analysis to Characterize the Plasma Concentration-time Course for Nepadutant in Infant With Colics From NIC-04 | 0.0275 fraction of dose absorbed |
| Cohort 2 | A Population Pharmacokinetic Analysis to Characterize the Plasma Concentration-time Course for Nepadutant in Infant With Colics From NIC-04 | 0.0342 fraction of dose absorbed |
| Cohort 1 | A Population Pharmacokinetic Analysis to Characterize the Plasma Concentration-time Course for Nepadutant in Infant With Colics From NIC-04 | 0.0346 fraction of dose absorbed |
Secondary
A Population Pharmacokinetic Analysis to Characterize the Plasma Concentration-time Course for Nepadutant in Infant With Colics From NIC-04
The population pharmacokinetic analyses is presented. PopPK Clearance estimated with a one compartment model with first order absorption and elimination.
Time frame: 0.5, 1, 2, 3 hours post Single Dose and 24 hours post Repeated Dose
Population: At visit 2, samples from 12 subjects in 0.1 mg/kg and from 15 subjects in 0.5 mg/kg.~At visit 3\*, 4\*: samples from 15 subjects in 0.1 - 0.5 mg/kg cohort, from 5 in 0.5 - 1 mg/kg cohort and from 6 in 0.1 - 1 mg/kg cohort.~\*N=26 instead of 27 as one patient early terminated the study
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cohort 3 | A Population Pharmacokinetic Analysis to Characterize the Plasma Concentration-time Course for Nepadutant in Infant With Colics From NIC-04 | 1.24 L/h |
| Cohort 2 | A Population Pharmacokinetic Analysis to Characterize the Plasma Concentration-time Course for Nepadutant in Infant With Colics From NIC-04 | 1.31 L/h |
| Cohort 1 | A Population Pharmacokinetic Analysis to Characterize the Plasma Concentration-time Course for Nepadutant in Infant With Colics From NIC-04 | 1.64 L/h |
Secondary
A Population Pharmacokinetic Analysis to Characterize the Plasma Concentration-time Course for Nepadutant in Infant With Colics From NIC-04
PopPK Volume estimated with a one compartment model with first order absorption and elimination. NOTE: for this measure, no inter-individual variability was estimated, therefore the value for each cohort corresponds to the typical value.
Time frame: 0.5, 1, 2, 3 hours post Single Dose and 24 hours post Repeated Dose
Population: At visit 2, samples from 6 subjects in Cohort 1 at 0.1mg/kg; 6 subjects in Cohort 3 at 0,1 mg/kg; 15 subjects in Cohort 2 at 0.5 mg/kg.~At visit 3\*, 4\*: samples from 5 subjects in Cohort 1 (0.1 - 0.5 mg/kg), 15 subjects in Cohort 2 (0.5 - 1 mg/kg) and 6 subjects in Cohort 3 (0.1 - 1 mg/kg).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cohort 3 | A Population Pharmacokinetic Analysis to Characterize the Plasma Concentration-time Course for Nepadutant in Infant With Colics From NIC-04 | 22.5 L |
Secondary
A Population Pharmacokinetic Analysis to Characterize the Plasma Concentration-time Course for Nepadutant in Infant With Colics From NIC-04
The population pharmacokinetic analyses is presented. PopPK Ka estimated with a one compartment model with first order absorption and elimination. NOTE: for this measure, no inter-individual variability was estimated, therefore the value for each cohort corresponds to the typical value.
Time frame: 0.5, 1, 2, 3 hours post Single Dose and 24 hours post Repeated Dose
Population: At visit 2, samples from 6 subjects in Cohort 1 at 0.1mg/kg; 6 subjects in Cohort 3 at 0,1 mg/kg; 15 subjects in Cohort 2 at 0.5 mg/kg.~At visit 3\*, 4\*: samples from 5 subjects in Cohort 1 (0.1 - 0.5 mg/kg), 15 subjects in Cohort 2 (0.5 - 1 mg/kg) and 6 subjects in Cohort 3 (0.1 - 1 mg/kg).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cohort 3 | A Population Pharmacokinetic Analysis to Characterize the Plasma Concentration-time Course for Nepadutant in Infant With Colics From NIC-04 | 206 1/h |
Secondary
Incidence and Severity of AEs_ Number of Adverse Events by Treatment Dose Level
The analysis is by treatment - Each infant was treated with two out of three ascending dose (0.1, 0.5 or 1.0 mg/kg), therefore counted in more than one dose level.
Time frame: up to 4 weeks
Population: All subjects who received at least one administration of study treatment including dose tolerability test (safety population)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 3 | Incidence and Severity of AEs_ Number of Adverse Events by Treatment Dose Level | General disorders and administration site conditio | 1 Number of events |
| Cohort 3 | Incidence and Severity of AEs_ Number of Adverse Events by Treatment Dose Level | Psychiatric disorders | 0 Number of events |
| Cohort 3 | Incidence and Severity of AEs_ Number of Adverse Events by Treatment Dose Level | Injury, poisoning and procedural complications | 1 Number of events |
| Cohort 3 | Incidence and Severity of AEs_ Number of Adverse Events by Treatment Dose Level | gastrointestinal disorder | 6 Number of events |
| Cohort 3 | Incidence and Severity of AEs_ Number of Adverse Events by Treatment Dose Level | Skin and subcutaneous tissue disorders | 3 Number of events |
| Cohort 3 | Incidence and Severity of AEs_ Number of Adverse Events by Treatment Dose Level | Respiratory, thoracic and medistinal disorders | 3 Number of events |
| Cohort 3 | Incidence and Severity of AEs_ Number of Adverse Events by Treatment Dose Level | Infections and infestations | 7 Number of events |
| Cohort 2 | Incidence and Severity of AEs_ Number of Adverse Events by Treatment Dose Level | Injury, poisoning and procedural complications | 1 Number of events |
| Cohort 2 | Incidence and Severity of AEs_ Number of Adverse Events by Treatment Dose Level | gastrointestinal disorder | 4 Number of events |
| Cohort 2 | Incidence and Severity of AEs_ Number of Adverse Events by Treatment Dose Level | General disorders and administration site conditio | 0 Number of events |
| Cohort 2 | Incidence and Severity of AEs_ Number of Adverse Events by Treatment Dose Level | Infections and infestations | 2 Number of events |
| Cohort 2 | Incidence and Severity of AEs_ Number of Adverse Events by Treatment Dose Level | Psychiatric disorders | 0 Number of events |
| Cohort 2 | Incidence and Severity of AEs_ Number of Adverse Events by Treatment Dose Level | Respiratory, thoracic and medistinal disorders | 1 Number of events |
| Cohort 2 | Incidence and Severity of AEs_ Number of Adverse Events by Treatment Dose Level | Skin and subcutaneous tissue disorders | 1 Number of events |
| Cohort 1 | Incidence and Severity of AEs_ Number of Adverse Events by Treatment Dose Level | Psychiatric disorders | 1 Number of events |
| Cohort 1 | Incidence and Severity of AEs_ Number of Adverse Events by Treatment Dose Level | General disorders and administration site conditio | 0 Number of events |
| Cohort 1 | Incidence and Severity of AEs_ Number of Adverse Events by Treatment Dose Level | Skin and subcutaneous tissue disorders | 3 Number of events |
| Cohort 1 | Incidence and Severity of AEs_ Number of Adverse Events by Treatment Dose Level | Respiratory, thoracic and medistinal disorders | 1 Number of events |
| Cohort 1 | Incidence and Severity of AEs_ Number of Adverse Events by Treatment Dose Level | Injury, poisoning and procedural complications | 0 Number of events |
| Cohort 1 | Incidence and Severity of AEs_ Number of Adverse Events by Treatment Dose Level | Infections and infestations | 1 Number of events |
| Cohort 1 | Incidence and Severity of AEs_ Number of Adverse Events by Treatment Dose Level | gastrointestinal disorder | 3 Number of events |