Trial Outcomes & Findings for Safety, Pharmacokinetics (PK), and Efficacy of Buprenorphine Transdermal System (BTDS) in Children (NCT NCT01324570)

Last Updated: 2017-07-06

Results Overview

Safety assessments consisted of reports of AEs, vital signs (blood pressure, pulse rate, respiratory rate, and temperature), weight, hemoglobin-oxygen saturation measured by pulse oximetry (SpO2), clinical laboratory tests, somnolence (assessed by the University of Michigan Sedation Scale \[UMSS\]), conventional 12-lead electrocardiograms (ECGs), and 24-hour digital 12-lead ECGs (Holter monitor). Safety variables were summarized descriptively within age group for the safety population.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

41 participants

Primary outcome timeframe

Up to 28 weeks

Results posted on

2017-07-06

Participant Flow

First Patient First Visit: 23-July-2012; Last Patient Last Visit: 23-May-2016. The study was conducted at 33 study centers in the United States

Participant milestones

Participant milestones
Measure	7 to 11 Years Children 7 to 11 years of age	12 to 16 Years Children 12 to 16 years of age
Overall Study STARTED	6	35
Overall Study COMPLETED	2	21
Overall Study NOT COMPLETED	4	14

Reasons for withdrawal

Reasons for withdrawal
Measure	7 to 11 Years Children 7 to 11 years of age	12 to 16 Years Children 12 to 16 years of age
Overall Study Adverse Event	4	7
Overall Study Withdrawal by Subject	0	3
Overall Study Lack of Efficacy	0	1
Overall Study Confirmed or suspected diversion	0	1
Overall Study Administrative	0	2

Baseline Characteristics

Safety, Pharmacokinetics (PK), and Efficacy of Buprenorphine Transdermal System (BTDS) in Children

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	7 to 11 Years n=6 Participants Children 7 to 11 years of age	12 to 16 Years n=35 Participants Children 12 to 16 years of age	Total n=41 Participants Total of all reporting groups
Age, Continuous	10.3 years STANDARD_DEVIATION 1.21 • n=5 Participants	14.6 years STANDARD_DEVIATION 1.31 • n=7 Participants	14.0 years STANDARD_DEVIATION 1.99 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	23 Participants n=7 Participants	26 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	12 Participants n=7 Participants	15 Participants n=5 Participants
Race/Ethnicity, Customized White	3 Participants n=5 Participants	18 Participants n=7 Participants	21 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	2 Participants n=5 Participants	15 Participants n=7 Participants	17 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 28 weeks

Population: The safety population (N=41) was the group of patients who received at least 1 dose of study drug during the study.

Outcome measures

Outcome measures
Measure	7 to 11 Years n=6 Participants Children 7 to 11 years of age	12 to 16 Years n=35 Participants Children 12 to 16 years of age
The Number of Participants With Adverse Events as a Measure of Safety Serious adverse events	5 Participants	5 Participants
The Number of Participants With Adverse Events as a Measure of Safety All other adverse events in ≥ 5% of patients	6 Participants	20 Participants

PRIMARY outcome

Timeframe: Day 1, end of week 1, days 9/10, end of week 2, and end of week 4 or at discontinuation prior to end of study visit

Population: The full analysis population (FAP) for PK consisted of patients who received study drug and had at least 1 valid quantifiable PK blood sample (N=41).Three patients had no quantifiable plasma buprenorphine concentration measurements and were not included in the PK analysis.The final buprenorphine pediatric PK analysis dataset comprised 38 patients.

The population PK (PopPK) of BTDS buprenorphine in pediatric patients ages 7 to 16 years was described by a 2-compartment model with sequential zero- and first-order absorption from the patch. A fixed allometric relationship was used to describe the effects of changes in ideal body weight (IBW) across pediatric patients on all clearance and volume parameters. Given the sparse sample collections, small sample size, and complexity of the absorption process with the patch formulation, this PopPK model was fit to the pediatric data using nonlinear mixed effects modeling (NONMEM) Bayes method with selective use of priors from previous adult PopPK results. Estimates of fixed effects from the final model were used to calculate the CL/F after patch dosing given the covariate distribution in the PopPK dataset and the typical weights from children in the National Health and Nutrition Examination Survey (NHANES) dataset.

Outcome measures

Outcome measures
Measure	7 to 11 Years n=38 Participants Children 7 to 11 years of age	12 to 16 Years Children 12 to 16 years of age
Pharmacokinetics (PK) of Buprenorphine Following Transdermal Administration: Apparent Clearance (CL/F)	293 Liters/hour Interval 264.0 to 326.0	—

PRIMARY outcome

Timeframe: Day 1, end of week 1, days 9/10, end of week 2, and end of week 4 or at discontinuation prior to end of study visit

The population PK (PopPK) of BTDS buprenorphine in pediatric patients ages 7 to 16 years was described by a 2-compartment model with sequential zero- and first-order absorption from the patch. A fixed allometric relationship was used to describe the effects of changes in ideal body weight (IBW) across pediatric patients on all clearance and volume parameters. Given the sparse sample collections, small sample size, and complexity of the absorption process with the patch formulation, this PopPK model was fit to the pediatric data using nonlinear mixed effects modeling (NONMEM) Bayes method with selective use of priors from previous adult PopPK results. Estimates of fixed effects from the final model were used to calculate the Vc/F after patch dosing given the covariate distribution in the PopPK dataset and the typical weights from children in the National Health and Nutrition Examination Survey (NHANES) dataset.

Outcome measures

Outcome measures
Measure	7 to 11 Years n=38 Participants Children 7 to 11 years of age	12 to 16 Years Children 12 to 16 years of age
Pharmacokinetics (PK) of Buprenorphine Following Transdermal Administration: Apparent Volume of Distribution (Vc/F)	2350 Liters Interval 1950.0 to 2820.0	—

SECONDARY outcome

Timeframe: Up to 24 weeks

Population: The full analysis population (FAP) was the group of patients who received at least 1 dose of the study drug during the study.

Pain right now was assessed using the Faces of Pain Scale-Revised (FPS-R). The FPS-R is a horizontal row of 6 faces representing pain intensity, with "no hurt" at the far left and "hurts worst" at the far right; the intensities are scored as 0, 2, 4, 6, 8, or 10. A score of 0=no pain, and 10=very much pain. For screening to week 4, pain right now was assessed at 30 minutes before initial BTDS application on day 1; one hour after initial BTDS application on day 1; thereafter, once daily at approximately 8 PM for the first 4 weeks. Baseline score was the last assessment prior to the first dose. For weeks 1-4, weekly averages of the pain right now scores were calculated using the sum of all available pain right now scores recorded daily during a given week divided by the number of available scores. The study measured pain right now for weeks 6-24 once a week at approximately 8 PM while on treatment; however, no patients in this age group were treated beyond week 12.

Outcome measures

Outcome measures
Measure	7 to 11 Years n=5 Participants Children 7 to 11 years of age	12 to 16 Years Children 12 to 16 years of age
Pain Right Now Assessment by Patients Aged 7 to 11 Years, Inclusive Baseline	2.80 units on a scale Standard Error 1.497	—
Pain Right Now Assessment by Patients Aged 7 to 11 Years, Inclusive Week 1	3.49 units on a scale Standard Error 1.768	—
Pain Right Now Assessment by Patients Aged 7 to 11 Years, Inclusive Week 2	2.98 units on a scale Standard Error 1.871	—
Pain Right Now Assessment by Patients Aged 7 to 11 Years, Inclusive Week 3	0.29 units on a scale Standard Error 0.000	—
Pain Right Now Assessment by Patients Aged 7 to 11 Years, Inclusive Week 4	0.00 units on a scale Standard Error 0.000	—
Pain Right Now Assessment by Patients Aged 7 to 11 Years, Inclusive Week 5	0.00 units on a scale Standard Error NA Since only one patient reported a pain score, standard error was not calculated.	—
Pain Right Now Assessment by Patients Aged 7 to 11 Years, Inclusive Week 6	0.00 units on a scale Standard Error NA Since only one patient reported a pain score, standard error was not calculated.	—
Pain Right Now Assessment by Patients Aged 7 to 11 Years, Inclusive Week 7	0.00 units on a scale Standard Error NA Since only one patient reported a pain score, standard error was not calculated.	—
Pain Right Now Assessment by Patients Aged 7 to 11 Years, Inclusive Week 8	0.00 units on a scale Standard Error NA Since only one patient reported a pain score, standard error was not calculated.	—
Pain Right Now Assessment by Patients Aged 7 to 11 Years, Inclusive Week 9	0.00 units on a scale Standard Error NA Since only one patient reported a pain score, standard error was not calculated.	—
Pain Right Now Assessment by Patients Aged 7 to 11 Years, Inclusive Week 10	0.00 units on a scale Standard Error NA Since only one patient reported a pain score, standard error was not calculated.	—
Pain Right Now Assessment by Patients Aged 7 to 11 Years, Inclusive Week 11	0.00 units on a scale Standard Error NA Since only one patient reported a pain score, standard error was not calculated.	—
Pain Right Now Assessment by Patients Aged 7 to 11 Years, Inclusive Week 12	0.00 units on a scale Standard Error NA Since only one patient reported a pain score, standard error was not calculated.	—

SECONDARY outcome

Timeframe: Up to 24 weeks

Population: The FAP was the group of patients who received at least 1 dose of the study drug during the study.

Pain right now was assessed using a 100-mm visual analogue scale (VAS). The 100-mm VAS is a 100-mm line with 1 end marked as "no pain" and the other marked as "pain as bad as it could be." The patient was asked to make a mark on that line indicating his or her level of pain. Pain right now score was defined as the distance (in mm) from the "no pain" end to the patient's mark; 0=no pain and bigger numbers indicate more pain. For screening to week 4, pain right now was assessed 30 minutes before initial BTDS application on day 1; one hour after initial BTDS application on day 1; thereafter, once daily at approximately 8 PM for the first 4 weeks. Baseline was the last assessment prior to the first dose. For weeks 1-4, weekly averages of the pain right now scores were calculated using the sum of all available pain right now scores recorded daily during a given week divided by the number of available scores. For weeks 6-24, pain right now was measured once a week at approximately 8 PM.

Outcome measures

Outcome measures
Measure	7 to 11 Years n=35 Participants Children 7 to 11 years of age	12 to 16 Years Children 12 to 16 years of age
Pain Right Now Assessment by Patients Aged 12 to 16 Years, Inclusive Week 11	35.7 units on a scale Standard Error 8.15	—
Pain Right Now Assessment by Patients Aged 12 to 16 Years, Inclusive Week 12	42.5 units on a scale Standard Error 8.31	—
Pain Right Now Assessment by Patients Aged 12 to 16 Years, Inclusive Week 13	36.0 units on a scale Standard Error 7.99	—
Pain Right Now Assessment by Patients Aged 12 to 16 Years, Inclusive Week 14	38.2 units on a scale Standard Error 8.67	—
Pain Right Now Assessment by Patients Aged 12 to 16 Years, Inclusive Week 17	30.9 units on a scale Standard Error 5.74	—
Pain Right Now Assessment by Patients Aged 12 to 16 Years, Inclusive Week 18	37.7 units on a scale Standard Error 6.88	—
Pain Right Now Assessment by Patients Aged 12 to 16 Years, Inclusive Week 19	37.4 units on a scale Standard Error 5.50	—
Pain Right Now Assessment by Patients Aged 12 to 16 Years, Inclusive Week 20	35.6 units on a scale Standard Error 7.48	—
Pain Right Now Assessment by Patients Aged 12 to 16 Years, Inclusive Baseline	46.6 units on a scale Standard Error 4.55	—
Pain Right Now Assessment by Patients Aged 12 to 16 Years, Inclusive Week 1	43.1 units on a scale Standard Error 4.03	—
Pain Right Now Assessment by Patients Aged 12 to 16 Years, Inclusive Week 2	41.6 units on a scale Standard Error 4.67	—
Pain Right Now Assessment by Patients Aged 12 to 16 Years, Inclusive Week 3	36.0 units on a scale Standard Error 4.82	—
Pain Right Now Assessment by Patients Aged 12 to 16 Years, Inclusive Week 4	34.7 units on a scale Standard Error 5.09	—
Pain Right Now Assessment by Patients Aged 12 to 16 Years, Inclusive Week 5	30.3 units on a scale Standard Error 5.90	—
Pain Right Now Assessment by Patients Aged 12 to 16 Years, Inclusive Week 6	28.0 units on a scale Standard Error 6.56	—
Pain Right Now Assessment by Patients Aged 12 to 16 Years, Inclusive Week 7	29.1 units on a scale Standard Error 5.56	—
Pain Right Now Assessment by Patients Aged 12 to 16 Years, Inclusive Week 8	34.3 units on a scale Standard Error 7.17	—
Pain Right Now Assessment by Patients Aged 12 to 16 Years, Inclusive Week 9	27.3 units on a scale Standard Error 5.83	—
Pain Right Now Assessment by Patients Aged 12 to 16 Years, Inclusive Week 10	36.7 units on a scale Standard Error 5.83	—
Pain Right Now Assessment by Patients Aged 12 to 16 Years, Inclusive Week 15	30.5 units on a scale Standard Error 6.52	—
Pain Right Now Assessment by Patients Aged 12 to 16 Years, Inclusive Week 16	38.7 units on a scale Standard Error 6.94	—
Pain Right Now Assessment by Patients Aged 12 to 16 Years, Inclusive Week 21	32.4 units on a scale Standard Error 5.97	—
Pain Right Now Assessment by Patients Aged 12 to 16 Years, Inclusive Week 22	38.1 units on a scale Standard Error 5.84	—
Pain Right Now Assessment by Patients Aged 12 to 16 Years, Inclusive Week 23	38.7 units on a scale Standard Error 6.42	—
Pain Right Now Assessment by Patients Aged 12 to 16 Years, Inclusive Week 24	36.5 units on a scale Standard Error 5.35	—

SECONDARY outcome

Timeframe: End of treatment (week 24) or early discontinuation visit

Population: The full analysis population (FAP) (N=40) was the group of patients who received at least 1 dose of the study drug during the study; however data was provided for only 38 patients for this outcome measure.

The PGIC rating score variable was collected on a 7-point scale ranging from 1 to 7 (where 1 = very much improved; and 7 = very much worse). The PGIC is designed to assess overall satisfaction with the treatment. The PGIC score was summarized using the number and percent of patients in each of the 7 possible response categories overall and by age group. PGIC was assessed by the parent/caregiver at the end of treatment visit or early discontinuation visit.

Outcome measures

Outcome measures
Measure	7 to 11 Years n=4 Participants Children 7 to 11 years of age	12 to 16 Years n=34 Participants Children 12 to 16 years of age
Parent/Caregiver-assessed Global Impression of Change (PGIC) 5 = Minimally worse	1 Participants	2 Participants
Parent/Caregiver-assessed Global Impression of Change (PGIC) 6 = Much worse	0 Participants	1 Participants
Parent/Caregiver-assessed Global Impression of Change (PGIC) Participants Represented	4 Participants	34 Participants
Parent/Caregiver-assessed Global Impression of Change (PGIC) 1 = Very much improved	1 Participants	6 Participants
Parent/Caregiver-assessed Global Impression of Change (PGIC) 2 = Much improved	0 Participants	12 Participants
Parent/Caregiver-assessed Global Impression of Change (PGIC) 3 = Minimally improved	0 Participants	8 Participants
Parent/Caregiver-assessed Global Impression of Change (PGIC) 4 = No change	2 Participants	5 Participants
Parent/Caregiver-assessed Global Impression of Change (PGIC) 7 = Very much worse	0 Participants	0 Participants

Adverse Events

7 to 11 Years

Serious events: 5 serious events

Other events: 6 other events

Deaths: 0 deaths

12 to 16 Years

Serious events: 5 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	7 to 11 Years n=6 participants at risk Children 7 to 11 years of age	12 to 16 Years n=35 participants at risk Children 12 to 16 years of age
Blood and lymphatic system disorders Anaemia	16.7% 1/6 • Non-serious treatment-emergent adverse events (TEAEs) were collected from the initiation of treatment with study drug up to 7 days after the last dose of study drug. Serious adverse events (SAEs) were collected from the signing of the informed consent form through 30 days of the last dose of study drug. For the assessment of SAEs and TEAEs, the analysis population included all patients exposed to at least 1 dose of study drug (ie, safety population). An SAE of pneumohemothorax occurred in 1 patient during screening and an SAE of sickle cell pain crisis occurred in 1 patient during screening. Both patients were considered screen failures, were not treated with study drug, and were not included in the safety population.	0.00% 0/35 • Non-serious treatment-emergent adverse events (TEAEs) were collected from the initiation of treatment with study drug up to 7 days after the last dose of study drug. Serious adverse events (SAEs) were collected from the signing of the informed consent form through 30 days of the last dose of study drug. For the assessment of SAEs and TEAEs, the analysis population included all patients exposed to at least 1 dose of study drug (ie, safety population). An SAE of pneumohemothorax occurred in 1 patient during screening and an SAE of sickle cell pain crisis occurred in 1 patient during screening. Both patients were considered screen failures, were not treated with study drug, and were not included in the safety population.
Cardiac disorders Atrioventricular Block First Degree	16.7% 1/6 • Non-serious treatment-emergent adverse events (TEAEs) were collected from the initiation of treatment with study drug up to 7 days after the last dose of study drug. Serious adverse events (SAEs) were collected from the signing of the informed consent form through 30 days of the last dose of study drug. For the assessment of SAEs and TEAEs, the analysis population included all patients exposed to at least 1 dose of study drug (ie, safety population). An SAE of pneumohemothorax occurred in 1 patient during screening and an SAE of sickle cell pain crisis occurred in 1 patient during screening. Both patients were considered screen failures, were not treated with study drug, and were not included in the safety population.	0.00% 0/35 • Non-serious treatment-emergent adverse events (TEAEs) were collected from the initiation of treatment with study drug up to 7 days after the last dose of study drug. Serious adverse events (SAEs) were collected from the signing of the informed consent form through 30 days of the last dose of study drug. For the assessment of SAEs and TEAEs, the analysis population included all patients exposed to at least 1 dose of study drug (ie, safety population). An SAE of pneumohemothorax occurred in 1 patient during screening and an SAE of sickle cell pain crisis occurred in 1 patient during screening. Both patients were considered screen failures, were not treated with study drug, and were not included in the safety population.
Congenital, familial and genetic disorders Hereditary Angioedema	0.00% 0/6 • Non-serious treatment-emergent adverse events (TEAEs) were collected from the initiation of treatment with study drug up to 7 days after the last dose of study drug. Serious adverse events (SAEs) were collected from the signing of the informed consent form through 30 days of the last dose of study drug. For the assessment of SAEs and TEAEs, the analysis population included all patients exposed to at least 1 dose of study drug (ie, safety population). An SAE of pneumohemothorax occurred in 1 patient during screening and an SAE of sickle cell pain crisis occurred in 1 patient during screening. Both patients were considered screen failures, were not treated with study drug, and were not included in the safety population.	2.9% 1/35 • Non-serious treatment-emergent adverse events (TEAEs) were collected from the initiation of treatment with study drug up to 7 days after the last dose of study drug. Serious adverse events (SAEs) were collected from the signing of the informed consent form through 30 days of the last dose of study drug. For the assessment of SAEs and TEAEs, the analysis population included all patients exposed to at least 1 dose of study drug (ie, safety population). An SAE of pneumohemothorax occurred in 1 patient during screening and an SAE of sickle cell pain crisis occurred in 1 patient during screening. Both patients were considered screen failures, were not treated with study drug, and were not included in the safety population.
Congenital, familial and genetic disorders Sickle Cell Anaemia With Crisis	0.00% 0/6 • Non-serious treatment-emergent adverse events (TEAEs) were collected from the initiation of treatment with study drug up to 7 days after the last dose of study drug. Serious adverse events (SAEs) were collected from the signing of the informed consent form through 30 days of the last dose of study drug. For the assessment of SAEs and TEAEs, the analysis population included all patients exposed to at least 1 dose of study drug (ie, safety population). An SAE of pneumohemothorax occurred in 1 patient during screening and an SAE of sickle cell pain crisis occurred in 1 patient during screening. Both patients were considered screen failures, were not treated with study drug, and were not included in the safety population.	5.7% 2/35 • Non-serious treatment-emergent adverse events (TEAEs) were collected from the initiation of treatment with study drug up to 7 days after the last dose of study drug. Serious adverse events (SAEs) were collected from the signing of the informed consent form through 30 days of the last dose of study drug. For the assessment of SAEs and TEAEs, the analysis population included all patients exposed to at least 1 dose of study drug (ie, safety population). An SAE of pneumohemothorax occurred in 1 patient during screening and an SAE of sickle cell pain crisis occurred in 1 patient during screening. Both patients were considered screen failures, were not treated with study drug, and were not included in the safety population.
Gastrointestinal disorders Crohn's Disease	16.7% 1/6 • Non-serious treatment-emergent adverse events (TEAEs) were collected from the initiation of treatment with study drug up to 7 days after the last dose of study drug. Serious adverse events (SAEs) were collected from the signing of the informed consent form through 30 days of the last dose of study drug. For the assessment of SAEs and TEAEs, the analysis population included all patients exposed to at least 1 dose of study drug (ie, safety population). An SAE of pneumohemothorax occurred in 1 patient during screening and an SAE of sickle cell pain crisis occurred in 1 patient during screening. Both patients were considered screen failures, were not treated with study drug, and were not included in the safety population.	0.00% 0/35 • Non-serious treatment-emergent adverse events (TEAEs) were collected from the initiation of treatment with study drug up to 7 days after the last dose of study drug. Serious adverse events (SAEs) were collected from the signing of the informed consent form through 30 days of the last dose of study drug. For the assessment of SAEs and TEAEs, the analysis population included all patients exposed to at least 1 dose of study drug (ie, safety population). An SAE of pneumohemothorax occurred in 1 patient during screening and an SAE of sickle cell pain crisis occurred in 1 patient during screening. Both patients were considered screen failures, were not treated with study drug, and were not included in the safety population.
General disorders Fatigue	16.7% 1/6 • Non-serious treatment-emergent adverse events (TEAEs) were collected from the initiation of treatment with study drug up to 7 days after the last dose of study drug. Serious adverse events (SAEs) were collected from the signing of the informed consent form through 30 days of the last dose of study drug. For the assessment of SAEs and TEAEs, the analysis population included all patients exposed to at least 1 dose of study drug (ie, safety population). An SAE of pneumohemothorax occurred in 1 patient during screening and an SAE of sickle cell pain crisis occurred in 1 patient during screening. Both patients were considered screen failures, were not treated with study drug, and were not included in the safety population.	0.00% 0/35 • Non-serious treatment-emergent adverse events (TEAEs) were collected from the initiation of treatment with study drug up to 7 days after the last dose of study drug. Serious adverse events (SAEs) were collected from the signing of the informed consent form through 30 days of the last dose of study drug. For the assessment of SAEs and TEAEs, the analysis population included all patients exposed to at least 1 dose of study drug (ie, safety population). An SAE of pneumohemothorax occurred in 1 patient during screening and an SAE of sickle cell pain crisis occurred in 1 patient during screening. Both patients were considered screen failures, were not treated with study drug, and were not included in the safety population.
Infections and infestations Appendicitis	16.7% 1/6 • Non-serious treatment-emergent adverse events (TEAEs) were collected from the initiation of treatment with study drug up to 7 days after the last dose of study drug. Serious adverse events (SAEs) were collected from the signing of the informed consent form through 30 days of the last dose of study drug. For the assessment of SAEs and TEAEs, the analysis population included all patients exposed to at least 1 dose of study drug (ie, safety population). An SAE of pneumohemothorax occurred in 1 patient during screening and an SAE of sickle cell pain crisis occurred in 1 patient during screening. Both patients were considered screen failures, were not treated with study drug, and were not included in the safety population.	0.00% 0/35 • Non-serious treatment-emergent adverse events (TEAEs) were collected from the initiation of treatment with study drug up to 7 days after the last dose of study drug. Serious adverse events (SAEs) were collected from the signing of the informed consent form through 30 days of the last dose of study drug. For the assessment of SAEs and TEAEs, the analysis population included all patients exposed to at least 1 dose of study drug (ie, safety population). An SAE of pneumohemothorax occurred in 1 patient during screening and an SAE of sickle cell pain crisis occurred in 1 patient during screening. Both patients were considered screen failures, were not treated with study drug, and were not included in the safety population.
Infections and infestations Osteomyelitis Chronic	0.00% 0/6 • Non-serious treatment-emergent adverse events (TEAEs) were collected from the initiation of treatment with study drug up to 7 days after the last dose of study drug. Serious adverse events (SAEs) were collected from the signing of the informed consent form through 30 days of the last dose of study drug. For the assessment of SAEs and TEAEs, the analysis population included all patients exposed to at least 1 dose of study drug (ie, safety population). An SAE of pneumohemothorax occurred in 1 patient during screening and an SAE of sickle cell pain crisis occurred in 1 patient during screening. Both patients were considered screen failures, were not treated with study drug, and were not included in the safety population.	2.9% 1/35 • Non-serious treatment-emergent adverse events (TEAEs) were collected from the initiation of treatment with study drug up to 7 days after the last dose of study drug. Serious adverse events (SAEs) were collected from the signing of the informed consent form through 30 days of the last dose of study drug. For the assessment of SAEs and TEAEs, the analysis population included all patients exposed to at least 1 dose of study drug (ie, safety population). An SAE of pneumohemothorax occurred in 1 patient during screening and an SAE of sickle cell pain crisis occurred in 1 patient during screening. Both patients were considered screen failures, were not treated with study drug, and were not included in the safety population.
Metabolism and nutrition disorders Malnutrition	16.7% 1/6 • Non-serious treatment-emergent adverse events (TEAEs) were collected from the initiation of treatment with study drug up to 7 days after the last dose of study drug. Serious adverse events (SAEs) were collected from the signing of the informed consent form through 30 days of the last dose of study drug. For the assessment of SAEs and TEAEs, the analysis population included all patients exposed to at least 1 dose of study drug (ie, safety population). An SAE of pneumohemothorax occurred in 1 patient during screening and an SAE of sickle cell pain crisis occurred in 1 patient during screening. Both patients were considered screen failures, were not treated with study drug, and were not included in the safety population.	0.00% 0/35 • Non-serious treatment-emergent adverse events (TEAEs) were collected from the initiation of treatment with study drug up to 7 days after the last dose of study drug. Serious adverse events (SAEs) were collected from the signing of the informed consent form through 30 days of the last dose of study drug. For the assessment of SAEs and TEAEs, the analysis population included all patients exposed to at least 1 dose of study drug (ie, safety population). An SAE of pneumohemothorax occurred in 1 patient during screening and an SAE of sickle cell pain crisis occurred in 1 patient during screening. Both patients were considered screen failures, were not treated with study drug, and were not included in the safety population.
Musculoskeletal and connective tissue disorders Osteonecrosis	16.7% 1/6 • Non-serious treatment-emergent adverse events (TEAEs) were collected from the initiation of treatment with study drug up to 7 days after the last dose of study drug. Serious adverse events (SAEs) were collected from the signing of the informed consent form through 30 days of the last dose of study drug. For the assessment of SAEs and TEAEs, the analysis population included all patients exposed to at least 1 dose of study drug (ie, safety population). An SAE of pneumohemothorax occurred in 1 patient during screening and an SAE of sickle cell pain crisis occurred in 1 patient during screening. Both patients were considered screen failures, were not treated with study drug, and were not included in the safety population.	0.00% 0/35 • Non-serious treatment-emergent adverse events (TEAEs) were collected from the initiation of treatment with study drug up to 7 days after the last dose of study drug. Serious adverse events (SAEs) were collected from the signing of the informed consent form through 30 days of the last dose of study drug. For the assessment of SAEs and TEAEs, the analysis population included all patients exposed to at least 1 dose of study drug (ie, safety population). An SAE of pneumohemothorax occurred in 1 patient during screening and an SAE of sickle cell pain crisis occurred in 1 patient during screening. Both patients were considered screen failures, were not treated with study drug, and were not included in the safety population.
Nervous system disorders Hypersomnia	16.7% 1/6 • Non-serious treatment-emergent adverse events (TEAEs) were collected from the initiation of treatment with study drug up to 7 days after the last dose of study drug. Serious adverse events (SAEs) were collected from the signing of the informed consent form through 30 days of the last dose of study drug. For the assessment of SAEs and TEAEs, the analysis population included all patients exposed to at least 1 dose of study drug (ie, safety population). An SAE of pneumohemothorax occurred in 1 patient during screening and an SAE of sickle cell pain crisis occurred in 1 patient during screening. Both patients were considered screen failures, were not treated with study drug, and were not included in the safety population.	0.00% 0/35 • Non-serious treatment-emergent adverse events (TEAEs) were collected from the initiation of treatment with study drug up to 7 days after the last dose of study drug. Serious adverse events (SAEs) were collected from the signing of the informed consent form through 30 days of the last dose of study drug. For the assessment of SAEs and TEAEs, the analysis population included all patients exposed to at least 1 dose of study drug (ie, safety population). An SAE of pneumohemothorax occurred in 1 patient during screening and an SAE of sickle cell pain crisis occurred in 1 patient during screening. Both patients were considered screen failures, were not treated with study drug, and were not included in the safety population.
Nervous system disorders Migraine	0.00% 0/6 • Non-serious treatment-emergent adverse events (TEAEs) were collected from the initiation of treatment with study drug up to 7 days after the last dose of study drug. Serious adverse events (SAEs) were collected from the signing of the informed consent form through 30 days of the last dose of study drug. For the assessment of SAEs and TEAEs, the analysis population included all patients exposed to at least 1 dose of study drug (ie, safety population). An SAE of pneumohemothorax occurred in 1 patient during screening and an SAE of sickle cell pain crisis occurred in 1 patient during screening. Both patients were considered screen failures, were not treated with study drug, and were not included in the safety population.	2.9% 1/35 • Non-serious treatment-emergent adverse events (TEAEs) were collected from the initiation of treatment with study drug up to 7 days after the last dose of study drug. Serious adverse events (SAEs) were collected from the signing of the informed consent form through 30 days of the last dose of study drug. For the assessment of SAEs and TEAEs, the analysis population included all patients exposed to at least 1 dose of study drug (ie, safety population). An SAE of pneumohemothorax occurred in 1 patient during screening and an SAE of sickle cell pain crisis occurred in 1 patient during screening. Both patients were considered screen failures, were not treated with study drug, and were not included in the safety population.

Other adverse events

Additional Information

Clinical Leader

Purdue Pharma L.P.

Phone: 800-733-1333

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60