Trial Outcomes & Findings for CHF6563 in Babies With Neonatal Opioid Withdrawal Syndrome (NCT NCT04104646)

Last Updated: 2023-08-03

Results Overview

Duration of treatment defined as the number of hours from first dose of study drug administration until the last dose of study drug. Shown are results for the duration of treatment in all treated patients, regardless of discontinuation status, as well as those patients who completed the study (with non missing data). The number of subjects randomised in the study was much lower than planned. Although data from 5 subjects were used in the CHF6563 treatment group, only 2 subjects completed the study as planned i.e. 1 subject in each study arm; no imputation of missing or incomplete data was possible according to the methods defined in the study protocol and the SAP. No statistical analysis was performed.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

7 participants

Primary outcome timeframe

Up to 10 weeks after first dose

Results posted on

2023-08-03

Participant Flow

Participant milestones

Participant milestones
Measure	CHF6563 Sublingual dose of CHF6563 and the corresponding oral dose of morphine matched placebo	Morphine Oral dose of morphine and the corresponding sublingual dose of CHF6563 matched placebo
Overall Study STARTED	5	2
Overall Study COMPLETED	1	1
Overall Study NOT COMPLETED	4	1

Reasons for withdrawal

Reasons for withdrawal
Measure	CHF6563 Sublingual dose of CHF6563 and the corresponding oral dose of morphine matched placebo	Morphine Oral dose of morphine and the corresponding sublingual dose of CHF6563 matched placebo
Overall Study Withdrawal by Subject	1	1
Overall Study Lost to Follow-up	1	0
Overall Study Physician Decision	2	0

Baseline Characteristics

CHF6563 in Babies With Neonatal Opioid Withdrawal Syndrome

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	CHF6563 n=5 Participants Sublingual dose of CHF6563 and the corresponding oral dose of morphine matched placebo CHF6563: Sublingual CHF6563 administration at starting dose of 10 µg/kg q8 Morphine matched placebo: Oral morphine matched placebo administration	Morphine n=2 Participants Oral dose of morphine and the corresponding sublingual dose of CHF6563 matched placebo. Morphine: Oral morphine administration at starting dose of 0.07 mg/kg q4 CHF6563 matched placebo: Sublingual CHF6563 matched placebo administration	Total n=7 Participants Total of all reporting groups
Age, Continuous	1.0 days STANDARD_DEVIATION 0.7 • n=5 Participants	0.5 days STANDARD_DEVIATION 0.7 • n=7 Participants	0.9 days STANDARD_DEVIATION 0.7 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	5 participants n=5 Participants	2 participants n=7 Participants	7 participants n=5 Participants
Gestational age	38.37 weeks STANDARD_DEVIATION 1.17 • n=5 Participants	39.14 weeks STANDARD_DEVIATION 1.62 • n=7 Participants	38.59 weeks STANDARD_DEVIATION 1.22 • n=5 Participants
Body length	49.16 cm STANDARD_DEVIATION 2.37 • n=5 Participants	50.90 cm STANDARD_DEVIATION 0.14 • n=7 Participants	49.66 cm STANDARD_DEVIATION 2.12 • n=5 Participants
Weight	3.1718 kg STANDARD_DEVIATION 0.5319 • n=5 Participants	3.7980 kg STANDARD_DEVIATION 0.8669 • n=7 Participants	3.3507 kg STANDARD_DEVIATION 0.6382 • n=5 Participants
Head circumference	33.50 cm STANDARD_DEVIATION 1.12 • n=5 Participants	35.50 cm STANDARD_DEVIATION 2.12 • n=7 Participants	34.07 cm STANDARD_DEVIATION 1.59 • n=5 Participants

PRIMARY outcome

Timeframe: Up to 10 weeks after first dose

Population: Randomised Set: All randomised subjects. Only 7 subjects were randomised into the study; 2 subjects completed the study as planned; therefore, no statistical analysis was performed. Due to low recruitment rate, the study was terminated early for non-safety reasons.

Outcome measures

Outcome measures
Measure	CHF6563 n=5 Participants Sublingual dose of CHF6563 and the corresponding oral dose of morphine matched placebo CHF6563	Morphine n=2 Participants Oral dose of morphine and the corresponding sublingual dose of CHF6563 matched placebo.
Duration of Treatment All treated patients	157.62 hours Interval 3.8 to 547.7	570.85 hours Interval 501.5 to 640.2
Duration of Treatment Patients who completed the study (With Non Missing Data)	547.7 hours Interval 547.7 to 547.7	501.5 hours Interval 501.5 to 501.5

SECONDARY outcome

Timeframe: up to 10 weeks after first dose

Record the time to first weaning, defined as the number of hours from first dose of study drug administration until the first dose reduction. The number of subjects randomised in the study was much lower than planned. Although data from 5 subjects were used in the CHF6563 treatment group, only 2 subjects completed the study as planned i.e. 1 subject in each study arm; no imputation of missing or incomplete data was possible according to the methods defined in the study protocol and the SAP. No statistical analysis was performed.

Outcome measures

Outcome measures
Measure	CHF6563 n=5 Participants Sublingual dose of CHF6563 and the corresponding oral dose of morphine matched placebo CHF6563	Morphine n=2 Participants Oral dose of morphine and the corresponding sublingual dose of CHF6563 matched placebo.
Time to First Weaning All Treated Patients	120.3 hours Interval 120.3 to 120.3	56.2 hours Interval 40.4 to 72.0
Time to First Weaning Patients who completed the study (With Non Missing Data)	120.3 hours Interval 120.3 to 120.3	72 hours Interval 72.0 to 72.0

SECONDARY outcome

Timeframe: up to 10 weeks after first dose

Record the requirement for adjunctive drug therapy (phenobarbital) for signs of NOWS, recorded as Yes/No. Overall, 1 subject in the CHF6563 group and zero subjects in the morphine were reported as having received adjunctive drug therapy with phenobarbital. The number of subjects randomised in the study was much lower than planned. No imputation of missing or incomplete data was made. No statistical analysis was performed. NOWS=Neonatal Opioid Withdrawal Syndrome

Outcome measures

Outcome measures
Measure	CHF6563 n=5 Participants Sublingual dose of CHF6563 and the corresponding oral dose of morphine matched placebo CHF6563	Morphine n=2 Participants Oral dose of morphine and the corresponding sublingual dose of CHF6563 matched placebo.
Adjunctive Therapy	1 Participants	0 Participants

SECONDARY outcome

Timeframe: up to 10 weeks after first dose

Requirement for rescue doses and number of rescue doses administered (CHF6563 or morphine); (yes/no). The number of subjects randomised in the study was lower than planned. No imputation of missing or incomplete data was made. No statistical analysis was performed.

Outcome measures

Outcome measures
Measure	CHF6563 n=5 Participants Sublingual dose of CHF6563 and the corresponding oral dose of morphine matched placebo CHF6563	Morphine n=2 Participants Oral dose of morphine and the corresponding sublingual dose of CHF6563 matched placebo.
Requirement for Rescue Doses (CHF6563 or Morphine) Requirement for rescue doses -- Yes	4 Participants	2 Participants
Requirement for Rescue Doses (CHF6563 or Morphine) Requirement for rescue doses -- No	1 Participants	0 Participants

SECONDARY outcome

Timeframe: up to 10 weeks after first dose

Number of rescue doses administered. The number of subjects randomised in the study was much lower than planned. Although data from 5 subjects were used in the CHF6563 treatment group, only 2 subjects completed the study as planned i.e. 1 subject in each study arm; no imputation of missing or incomplete data was possible according to the methods defined in the study protocol and the SAP. No statistical analysis was performed. At the discretion of the physician, a rescue dose of CHF6563 or morphine could be given during the up-titration phase or during the weaning phases to a neonate who had a single FNAST score ≥12. A rescue dose was not to be administered within 1 hour of the previous dose or 1 hour before the next scheduled dose. Rescue doses were the same as the previous dose.

Outcome measures

Outcome measures
Measure	CHF6563 n=5 Participants Sublingual dose of CHF6563 and the corresponding oral dose of morphine matched placebo CHF6563	Morphine n=2 Participants Oral dose of morphine and the corresponding sublingual dose of CHF6563 matched placebo.
Number of Rescue Doses Administered All Treated Patients	1.6 number of rescue doses Interval 0.0 to 4.0	3 number of rescue doses Interval 1.0 to 5.0
Number of Rescue Doses Administered Patients who completed the study (With Non Missing Data)	4 number of rescue doses Interval 4.0 to 4.0	1 number of rescue doses Interval 1.0 to 1.0

SECONDARY outcome

Timeframe: up to 10 weeks plus 48 hours

Length of opioid-related hospital stay was defined as number of days from day of birth until 48 hours after the final dose of drug treatment for NOWS. Reported data show the length of opioid-related hospital stay (defined as number of days from day of birth until 48 hours after the final dose of drug treatment for NOWS). The number of subjects randomised in the study was much lower than planned. Although data from 5 subjects were used in the CHF6563 treatment group, only 2 subjects completed the study as planned i.e. 1 subject in each study arm; no imputation of missing or incomplete data was possible according to the methods defined in the study protocol and the SAP. No statistical analysis was performed.

Outcome measures

Outcome measures
Measure	CHF6563 n=5 Participants Sublingual dose of CHF6563 and the corresponding oral dose of morphine matched placebo CHF6563	Morphine n=2 Participants Oral dose of morphine and the corresponding sublingual dose of CHF6563 matched placebo.
Length of Opioid-related Hospital Stay All Treated Patients	10.64 days Interval 3.9 to 27.0	29.5 days Interval 26.2 to 32.8
Length of Opioid-related Hospital Stay Patients who completed the study (With Non Missing Data)	27.0 days Interval 27.0 to 27.0	26.2 days Interval 26.2 to 26.2

SECONDARY outcome

Timeframe: up to 6 weeks after last dose

Relapse of NOWS, defined as experiencing recurrence of significant signs of withdrawal . Reported are subjects with experiencing a relapse. The number of subjects randomised in the study was much lower than planned. No imputation of missing or incomplete data was made. No statistical analysis was performed. NOWS=Neonatal Opioid Withdrawal Syndrome

Outcome measures

Outcome measures
Measure	CHF6563 n=5 Participants Sublingual dose of CHF6563 and the corresponding oral dose of morphine matched placebo CHF6563	Morphine n=2 Participants Oral dose of morphine and the corresponding sublingual dose of CHF6563 matched placebo.
Relapse of NOWS	1 Participants	0 Participants

Adverse Events

CHF6563

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Morphine

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	CHF6563 n=5 participants at risk Sublingual dose of CHF6563 and the corresponding oral dose of morphine matched placebo CHF6563: Sublingual CHF6563 administration at starting dose of 10 µg/kg q8 Morphine matched-placebo: Oral morphine-matched placebo administration	Morphine n=2 participants at risk Oral dose of morphine and the corresponding sublingual dose of CHF6563 matched placebo. Morphine: Oral morphine administration at starting dose of 0.07 mg/kg q4 CHF6563 matched-placebo: Sublingual CHF6563 matched-placebo administration
Gastrointestinal disorders Vomiting	20.0% 1/5 • Number of events 1 • AEs and serious AEs (SAEs) were collected from the time of informed consent signature or from the neonate's birth through treatment and follow-up (FU) period (48 h after last treatment). Daily phone calls with the primary caregiver was for the first 7 d; weekly phone contact was up to 6 weeks after the final opioid treatment dose. NOWS treatment duration depends on Finnegan Neonatal Abstinence Scoring Tool (FNAST) scores and differs for each neonate; the maximum length of treatment was 10 weeks. Pre-treatment AEs=From between informed consent and first study drug administration. Treatment-emergent adverse events (TEAE)=From on or after first administration of any study drug. Peri-dosing AEs=AEs occurring during or shortly after (i.e., within 10 minutes) administration of study drug. Post-treatment AEs=From on or after the start of the FU phase (i.e. \>48h after end of treatment). Ongoing AEs/SAEs were followed until the event resolved/stabilized, as acceptable to the Investigator.	0.00% 0/2 • AEs and serious AEs (SAEs) were collected from the time of informed consent signature or from the neonate's birth through treatment and follow-up (FU) period (48 h after last treatment). Daily phone calls with the primary caregiver was for the first 7 d; weekly phone contact was up to 6 weeks after the final opioid treatment dose. NOWS treatment duration depends on Finnegan Neonatal Abstinence Scoring Tool (FNAST) scores and differs for each neonate; the maximum length of treatment was 10 weeks. Pre-treatment AEs=From between informed consent and first study drug administration. Treatment-emergent adverse events (TEAE)=From on or after first administration of any study drug. Peri-dosing AEs=AEs occurring during or shortly after (i.e., within 10 minutes) administration of study drug. Post-treatment AEs=From on or after the start of the FU phase (i.e. \>48h after end of treatment). Ongoing AEs/SAEs were followed until the event resolved/stabilized, as acceptable to the Investigator.
Gastrointestinal disorders Flatulence	0.00% 0/5 • AEs and serious AEs (SAEs) were collected from the time of informed consent signature or from the neonate's birth through treatment and follow-up (FU) period (48 h after last treatment). Daily phone calls with the primary caregiver was for the first 7 d; weekly phone contact was up to 6 weeks after the final opioid treatment dose. NOWS treatment duration depends on Finnegan Neonatal Abstinence Scoring Tool (FNAST) scores and differs for each neonate; the maximum length of treatment was 10 weeks. Pre-treatment AEs=From between informed consent and first study drug administration. Treatment-emergent adverse events (TEAE)=From on or after first administration of any study drug. Peri-dosing AEs=AEs occurring during or shortly after (i.e., within 10 minutes) administration of study drug. Post-treatment AEs=From on or after the start of the FU phase (i.e. \>48h after end of treatment). Ongoing AEs/SAEs were followed until the event resolved/stabilized, as acceptable to the Investigator.	50.0% 1/2 • Number of events 1 • AEs and serious AEs (SAEs) were collected from the time of informed consent signature or from the neonate's birth through treatment and follow-up (FU) period (48 h after last treatment). Daily phone calls with the primary caregiver was for the first 7 d; weekly phone contact was up to 6 weeks after the final opioid treatment dose. NOWS treatment duration depends on Finnegan Neonatal Abstinence Scoring Tool (FNAST) scores and differs for each neonate; the maximum length of treatment was 10 weeks. Pre-treatment AEs=From between informed consent and first study drug administration. Treatment-emergent adverse events (TEAE)=From on or after first administration of any study drug. Peri-dosing AEs=AEs occurring during or shortly after (i.e., within 10 minutes) administration of study drug. Post-treatment AEs=From on or after the start of the FU phase (i.e. \>48h after end of treatment). Ongoing AEs/SAEs were followed until the event resolved/stabilized, as acceptable to the Investigator.
Infections and infestations Fungal infection	0.00% 0/5 • AEs and serious AEs (SAEs) were collected from the time of informed consent signature or from the neonate's birth through treatment and follow-up (FU) period (48 h after last treatment). Daily phone calls with the primary caregiver was for the first 7 d; weekly phone contact was up to 6 weeks after the final opioid treatment dose. NOWS treatment duration depends on Finnegan Neonatal Abstinence Scoring Tool (FNAST) scores and differs for each neonate; the maximum length of treatment was 10 weeks. Pre-treatment AEs=From between informed consent and first study drug administration. Treatment-emergent adverse events (TEAE)=From on or after first administration of any study drug. Peri-dosing AEs=AEs occurring during or shortly after (i.e., within 10 minutes) administration of study drug. Post-treatment AEs=From on or after the start of the FU phase (i.e. \>48h after end of treatment). Ongoing AEs/SAEs were followed until the event resolved/stabilized, as acceptable to the Investigator.	50.0% 1/2 • Number of events 1 • AEs and serious AEs (SAEs) were collected from the time of informed consent signature or from the neonate's birth through treatment and follow-up (FU) period (48 h after last treatment). Daily phone calls with the primary caregiver was for the first 7 d; weekly phone contact was up to 6 weeks after the final opioid treatment dose. NOWS treatment duration depends on Finnegan Neonatal Abstinence Scoring Tool (FNAST) scores and differs for each neonate; the maximum length of treatment was 10 weeks. Pre-treatment AEs=From between informed consent and first study drug administration. Treatment-emergent adverse events (TEAE)=From on or after first administration of any study drug. Peri-dosing AEs=AEs occurring during or shortly after (i.e., within 10 minutes) administration of study drug. Post-treatment AEs=From on or after the start of the FU phase (i.e. \>48h after end of treatment). Ongoing AEs/SAEs were followed until the event resolved/stabilized, as acceptable to the Investigator.
Infections and infestations Skin candida	0.00% 0/5 • AEs and serious AEs (SAEs) were collected from the time of informed consent signature or from the neonate's birth through treatment and follow-up (FU) period (48 h after last treatment). Daily phone calls with the primary caregiver was for the first 7 d; weekly phone contact was up to 6 weeks after the final opioid treatment dose. NOWS treatment duration depends on Finnegan Neonatal Abstinence Scoring Tool (FNAST) scores and differs for each neonate; the maximum length of treatment was 10 weeks. Pre-treatment AEs=From between informed consent and first study drug administration. Treatment-emergent adverse events (TEAE)=From on or after first administration of any study drug. Peri-dosing AEs=AEs occurring during or shortly after (i.e., within 10 minutes) administration of study drug. Post-treatment AEs=From on or after the start of the FU phase (i.e. \>48h after end of treatment). Ongoing AEs/SAEs were followed until the event resolved/stabilized, as acceptable to the Investigator.	50.0% 1/2 • Number of events 1 • AEs and serious AEs (SAEs) were collected from the time of informed consent signature or from the neonate's birth through treatment and follow-up (FU) period (48 h after last treatment). Daily phone calls with the primary caregiver was for the first 7 d; weekly phone contact was up to 6 weeks after the final opioid treatment dose. NOWS treatment duration depends on Finnegan Neonatal Abstinence Scoring Tool (FNAST) scores and differs for each neonate; the maximum length of treatment was 10 weeks. Pre-treatment AEs=From between informed consent and first study drug administration. Treatment-emergent adverse events (TEAE)=From on or after first administration of any study drug. Peri-dosing AEs=AEs occurring during or shortly after (i.e., within 10 minutes) administration of study drug. Post-treatment AEs=From on or after the start of the FU phase (i.e. \>48h after end of treatment). Ongoing AEs/SAEs were followed until the event resolved/stabilized, as acceptable to the Investigator.
Skin and subcutaneous tissue disorders Rash	0.00% 0/5 • AEs and serious AEs (SAEs) were collected from the time of informed consent signature or from the neonate's birth through treatment and follow-up (FU) period (48 h after last treatment). Daily phone calls with the primary caregiver was for the first 7 d; weekly phone contact was up to 6 weeks after the final opioid treatment dose. NOWS treatment duration depends on Finnegan Neonatal Abstinence Scoring Tool (FNAST) scores and differs for each neonate; the maximum length of treatment was 10 weeks. Pre-treatment AEs=From between informed consent and first study drug administration. Treatment-emergent adverse events (TEAE)=From on or after first administration of any study drug. Peri-dosing AEs=AEs occurring during or shortly after (i.e., within 10 minutes) administration of study drug. Post-treatment AEs=From on or after the start of the FU phase (i.e. \>48h after end of treatment). Ongoing AEs/SAEs were followed until the event resolved/stabilized, as acceptable to the Investigator.	50.0% 1/2 • Number of events 1 • AEs and serious AEs (SAEs) were collected from the time of informed consent signature or from the neonate's birth through treatment and follow-up (FU) period (48 h after last treatment). Daily phone calls with the primary caregiver was for the first 7 d; weekly phone contact was up to 6 weeks after the final opioid treatment dose. NOWS treatment duration depends on Finnegan Neonatal Abstinence Scoring Tool (FNAST) scores and differs for each neonate; the maximum length of treatment was 10 weeks. Pre-treatment AEs=From between informed consent and first study drug administration. Treatment-emergent adverse events (TEAE)=From on or after first administration of any study drug. Peri-dosing AEs=AEs occurring during or shortly after (i.e., within 10 minutes) administration of study drug. Post-treatment AEs=From on or after the start of the FU phase (i.e. \>48h after end of treatment). Ongoing AEs/SAEs were followed until the event resolved/stabilized, as acceptable to the Investigator.
Injury, poisoning and procedural complications Overdose	20.0% 1/5 • Number of events 1 • AEs and serious AEs (SAEs) were collected from the time of informed consent signature or from the neonate's birth through treatment and follow-up (FU) period (48 h after last treatment). Daily phone calls with the primary caregiver was for the first 7 d; weekly phone contact was up to 6 weeks after the final opioid treatment dose. NOWS treatment duration depends on Finnegan Neonatal Abstinence Scoring Tool (FNAST) scores and differs for each neonate; the maximum length of treatment was 10 weeks. Pre-treatment AEs=From between informed consent and first study drug administration. Treatment-emergent adverse events (TEAE)=From on or after first administration of any study drug. Peri-dosing AEs=AEs occurring during or shortly after (i.e., within 10 minutes) administration of study drug. Post-treatment AEs=From on or after the start of the FU phase (i.e. \>48h after end of treatment). Ongoing AEs/SAEs were followed until the event resolved/stabilized, as acceptable to the Investigator.	0.00% 0/2 • AEs and serious AEs (SAEs) were collected from the time of informed consent signature or from the neonate's birth through treatment and follow-up (FU) period (48 h after last treatment). Daily phone calls with the primary caregiver was for the first 7 d; weekly phone contact was up to 6 weeks after the final opioid treatment dose. NOWS treatment duration depends on Finnegan Neonatal Abstinence Scoring Tool (FNAST) scores and differs for each neonate; the maximum length of treatment was 10 weeks. Pre-treatment AEs=From between informed consent and first study drug administration. Treatment-emergent adverse events (TEAE)=From on or after first administration of any study drug. Peri-dosing AEs=AEs occurring during or shortly after (i.e., within 10 minutes) administration of study drug. Post-treatment AEs=From on or after the start of the FU phase (i.e. \>48h after end of treatment). Ongoing AEs/SAEs were followed until the event resolved/stabilized, as acceptable to the Investigator.
Metabolism and nutrition disorders Poor feeding infant	20.0% 1/5 • Number of events 1 • AEs and serious AEs (SAEs) were collected from the time of informed consent signature or from the neonate's birth through treatment and follow-up (FU) period (48 h after last treatment). Daily phone calls with the primary caregiver was for the first 7 d; weekly phone contact was up to 6 weeks after the final opioid treatment dose. NOWS treatment duration depends on Finnegan Neonatal Abstinence Scoring Tool (FNAST) scores and differs for each neonate; the maximum length of treatment was 10 weeks. Pre-treatment AEs=From between informed consent and first study drug administration. Treatment-emergent adverse events (TEAE)=From on or after first administration of any study drug. Peri-dosing AEs=AEs occurring during or shortly after (i.e., within 10 minutes) administration of study drug. Post-treatment AEs=From on or after the start of the FU phase (i.e. \>48h after end of treatment). Ongoing AEs/SAEs were followed until the event resolved/stabilized, as acceptable to the Investigator.	0.00% 0/2 • AEs and serious AEs (SAEs) were collected from the time of informed consent signature or from the neonate's birth through treatment and follow-up (FU) period (48 h after last treatment). Daily phone calls with the primary caregiver was for the first 7 d; weekly phone contact was up to 6 weeks after the final opioid treatment dose. NOWS treatment duration depends on Finnegan Neonatal Abstinence Scoring Tool (FNAST) scores and differs for each neonate; the maximum length of treatment was 10 weeks. Pre-treatment AEs=From between informed consent and first study drug administration. Treatment-emergent adverse events (TEAE)=From on or after first administration of any study drug. Peri-dosing AEs=AEs occurring during or shortly after (i.e., within 10 minutes) administration of study drug. Post-treatment AEs=From on or after the start of the FU phase (i.e. \>48h after end of treatment). Ongoing AEs/SAEs were followed until the event resolved/stabilized, as acceptable to the Investigator.
Nervous system disorders Somnolence	20.0% 1/5 • Number of events 1 • AEs and serious AEs (SAEs) were collected from the time of informed consent signature or from the neonate's birth through treatment and follow-up (FU) period (48 h after last treatment). Daily phone calls with the primary caregiver was for the first 7 d; weekly phone contact was up to 6 weeks after the final opioid treatment dose. NOWS treatment duration depends on Finnegan Neonatal Abstinence Scoring Tool (FNAST) scores and differs for each neonate; the maximum length of treatment was 10 weeks. Pre-treatment AEs=From between informed consent and first study drug administration. Treatment-emergent adverse events (TEAE)=From on or after first administration of any study drug. Peri-dosing AEs=AEs occurring during or shortly after (i.e., within 10 minutes) administration of study drug. Post-treatment AEs=From on or after the start of the FU phase (i.e. \>48h after end of treatment). Ongoing AEs/SAEs were followed until the event resolved/stabilized, as acceptable to the Investigator.	0.00% 0/2 • AEs and serious AEs (SAEs) were collected from the time of informed consent signature or from the neonate's birth through treatment and follow-up (FU) period (48 h after last treatment). Daily phone calls with the primary caregiver was for the first 7 d; weekly phone contact was up to 6 weeks after the final opioid treatment dose. NOWS treatment duration depends on Finnegan Neonatal Abstinence Scoring Tool (FNAST) scores and differs for each neonate; the maximum length of treatment was 10 weeks. Pre-treatment AEs=From between informed consent and first study drug administration. Treatment-emergent adverse events (TEAE)=From on or after first administration of any study drug. Peri-dosing AEs=AEs occurring during or shortly after (i.e., within 10 minutes) administration of study drug. Post-treatment AEs=From on or after the start of the FU phase (i.e. \>48h after end of treatment). Ongoing AEs/SAEs were followed until the event resolved/stabilized, as acceptable to the Investigator.
Musculoskeletal and connective tissue disorders Hypotonia neonatal	20.0% 1/5 • Number of events 1 • AEs and serious AEs (SAEs) were collected from the time of informed consent signature or from the neonate's birth through treatment and follow-up (FU) period (48 h after last treatment). Daily phone calls with the primary caregiver was for the first 7 d; weekly phone contact was up to 6 weeks after the final opioid treatment dose. NOWS treatment duration depends on Finnegan Neonatal Abstinence Scoring Tool (FNAST) scores and differs for each neonate; the maximum length of treatment was 10 weeks. Pre-treatment AEs=From between informed consent and first study drug administration. Treatment-emergent adverse events (TEAE)=From on or after first administration of any study drug. Peri-dosing AEs=AEs occurring during or shortly after (i.e., within 10 minutes) administration of study drug. Post-treatment AEs=From on or after the start of the FU phase (i.e. \>48h after end of treatment). Ongoing AEs/SAEs were followed until the event resolved/stabilized, as acceptable to the Investigator.	0.00% 0/2 • AEs and serious AEs (SAEs) were collected from the time of informed consent signature or from the neonate's birth through treatment and follow-up (FU) period (48 h after last treatment). Daily phone calls with the primary caregiver was for the first 7 d; weekly phone contact was up to 6 weeks after the final opioid treatment dose. NOWS treatment duration depends on Finnegan Neonatal Abstinence Scoring Tool (FNAST) scores and differs for each neonate; the maximum length of treatment was 10 weeks. Pre-treatment AEs=From between informed consent and first study drug administration. Treatment-emergent adverse events (TEAE)=From on or after first administration of any study drug. Peri-dosing AEs=AEs occurring during or shortly after (i.e., within 10 minutes) administration of study drug. Post-treatment AEs=From on or after the start of the FU phase (i.e. \>48h after end of treatment). Ongoing AEs/SAEs were followed until the event resolved/stabilized, as acceptable to the Investigator.
Gastrointestinal disorders Infantile vomiting	20.0% 1/5 • Number of events 1 • AEs and serious AEs (SAEs) were collected from the time of informed consent signature or from the neonate's birth through treatment and follow-up (FU) period (48 h after last treatment). Daily phone calls with the primary caregiver was for the first 7 d; weekly phone contact was up to 6 weeks after the final opioid treatment dose. NOWS treatment duration depends on Finnegan Neonatal Abstinence Scoring Tool (FNAST) scores and differs for each neonate; the maximum length of treatment was 10 weeks. Pre-treatment AEs=From between informed consent and first study drug administration. Treatment-emergent adverse events (TEAE)=From on or after first administration of any study drug. Peri-dosing AEs=AEs occurring during or shortly after (i.e., within 10 minutes) administration of study drug. Post-treatment AEs=From on or after the start of the FU phase (i.e. \>48h after end of treatment). Ongoing AEs/SAEs were followed until the event resolved/stabilized, as acceptable to the Investigator.	0.00% 0/2 • AEs and serious AEs (SAEs) were collected from the time of informed consent signature or from the neonate's birth through treatment and follow-up (FU) period (48 h after last treatment). Daily phone calls with the primary caregiver was for the first 7 d; weekly phone contact was up to 6 weeks after the final opioid treatment dose. NOWS treatment duration depends on Finnegan Neonatal Abstinence Scoring Tool (FNAST) scores and differs for each neonate; the maximum length of treatment was 10 weeks. Pre-treatment AEs=From between informed consent and first study drug administration. Treatment-emergent adverse events (TEAE)=From on or after first administration of any study drug. Peri-dosing AEs=AEs occurring during or shortly after (i.e., within 10 minutes) administration of study drug. Post-treatment AEs=From on or after the start of the FU phase (i.e. \>48h after end of treatment). Ongoing AEs/SAEs were followed until the event resolved/stabilized, as acceptable to the Investigator.
Skin and subcutaneous tissue disorders Dry skin	20.0% 1/5 • Number of events 1 • AEs and serious AEs (SAEs) were collected from the time of informed consent signature or from the neonate's birth through treatment and follow-up (FU) period (48 h after last treatment). Daily phone calls with the primary caregiver was for the first 7 d; weekly phone contact was up to 6 weeks after the final opioid treatment dose. NOWS treatment duration depends on Finnegan Neonatal Abstinence Scoring Tool (FNAST) scores and differs for each neonate; the maximum length of treatment was 10 weeks. Pre-treatment AEs=From between informed consent and first study drug administration. Treatment-emergent adverse events (TEAE)=From on or after first administration of any study drug. Peri-dosing AEs=AEs occurring during or shortly after (i.e., within 10 minutes) administration of study drug. Post-treatment AEs=From on or after the start of the FU phase (i.e. \>48h after end of treatment). Ongoing AEs/SAEs were followed until the event resolved/stabilized, as acceptable to the Investigator.	0.00% 0/2 • AEs and serious AEs (SAEs) were collected from the time of informed consent signature or from the neonate's birth through treatment and follow-up (FU) period (48 h after last treatment). Daily phone calls with the primary caregiver was for the first 7 d; weekly phone contact was up to 6 weeks after the final opioid treatment dose. NOWS treatment duration depends on Finnegan Neonatal Abstinence Scoring Tool (FNAST) scores and differs for each neonate; the maximum length of treatment was 10 weeks. Pre-treatment AEs=From between informed consent and first study drug administration. Treatment-emergent adverse events (TEAE)=From on or after first administration of any study drug. Peri-dosing AEs=AEs occurring during or shortly after (i.e., within 10 minutes) administration of study drug. Post-treatment AEs=From on or after the start of the FU phase (i.e. \>48h after end of treatment). Ongoing AEs/SAEs were followed until the event resolved/stabilized, as acceptable to the Investigator.

Additional Information

Clinical Trial Transparency

Chiesi Farmaceutici S.p.A.

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Results disclosure agreements

Principal investigator is a sponsor employee Chiesi can publish and/or present any results of this study at scientific meetings, and to submit the clinical trial data to national and international Regulatory Authorities. Chiesi reserves the right to use such data for industrial purposes. Investigators will inform Chiesi before using the results of the study for publication or presentation, and agree to provide the Sponsor with a copy of the proposed presentation. Data from individual study sites must not be published separately.
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Restriction type: OTHER