Trial Outcomes & Findings for A Study to Assess the Effect of a Single Dose of ASP8062 on the Multiple Dose Safety, Tolerability and Pharmacokinetics of Buprenorphine/Naloxone in Participants With Opioid Use Disorder (NCT NCT04447287)
NCT ID: NCT04447287
Last Updated: 2024-11-21
Results Overview
An AE is defined as any untoward medical occurrence in a participant administered an Investigational Product (IP) and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding; abnormal laboratory test result or other safety assessment, symptom, or disease temporally associated with the use of IP whether or not considered related to the IP. A treatment-emergent adverse event (TEAE) was defined as an AE with onset at any time from first dosing until last scheduled procedure. AEs were considered serious (SAEs) if the AE resulted in death, was life-threatening, resulted in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, resulted in congenital anomaly, or birth defect or required inpatient hospitalization or led to prolongation of hospitalization.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
23 participants
Primary outcome timeframe
From first dose of study drug up to end of study visit (up to day 27)
Results posted on
2024-11-21
Participant Flow
Participants who had opioid use disorder (OUD) were enrolled in this study. Participants were enrolled in one site in the United States.
Participants were randomized using a 2:1 ratio. Eligible participants who met inclusion criteria and none of the exclusion criteria were enrolled. A total of 74 participants entered the screening process and out of which 56 discontinued prior to randomization. Prior to randomization, participants entered a run-in period. A total of 23 participants entered the run-in period and 19 completed, 1 participant completed the run-in period but discontinued before randomization.
Participant milestones
| Measure |
Buprenorphine/Naloxone
Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. Participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
ASP8062 in Combination With Buprenorphine/Naloxone
Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. In the Investigational Period participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
Placebo ASP8062 in Combination With Buprenorphine/Naloxone
Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. In the Investigational Period participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. After randomization on day 12, participants received a single oral dose of placebo concomitantly with buprenorphine/naloxone. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
|---|---|---|---|
|
Period 1: Run-in Period
STARTED
|
23
|
0
|
0
|
|
Period 1: Run-in Period
COMPLETED
|
19
|
0
|
0
|
|
Period 1: Run-in Period
NOT COMPLETED
|
4
|
0
|
0
|
|
Period 2: Investigational Period
STARTED
|
1
|
12
|
6
|
|
Period 2: Investigational Period
COMPLETED
|
0
|
12
|
6
|
|
Period 2: Investigational Period
NOT COMPLETED
|
1
|
0
|
0
|
|
Period 3: Down-Titration Period
STARTED
|
0
|
12
|
6
|
|
Period 3: Down-Titration Period
COMPLETED
|
0
|
12
|
6
|
|
Period 3: Down-Titration Period
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Buprenorphine/Naloxone
Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. Participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
ASP8062 in Combination With Buprenorphine/Naloxone
Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. In the Investigational Period participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
Placebo ASP8062 in Combination With Buprenorphine/Naloxone
Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. In the Investigational Period participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. After randomization on day 12, participants received a single oral dose of placebo concomitantly with buprenorphine/naloxone. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
|---|---|---|---|
|
Period 1: Run-in Period
Adverse Event
|
3
|
0
|
0
|
|
Period 1: Run-in Period
Withdrawal by Subject
|
1
|
0
|
0
|
|
Period 2: Investigational Period
Completed the run-in period but discontinued before randomization due to limited samples collected.
|
1
|
0
|
0
|
Baseline Characteristics
The analysis population consisted of all participants who received at least 1 dose of IP during Run-in Period; Investigational Period and Down-titration Period.
Baseline characteristics by cohort
| Measure |
Buprenorphine/Naloxone
n=5 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. Participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
ASP8062 in Combination With Buprenorphine/Naloxone
n=12 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. In the Investigational Period participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
Placebo ASP8062 in Combination With Buprenorphine/Naloxone
n=6 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. In the Investigational Period participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. After randomization on day 12, participants received a single oral dose of placebo concomitantly with buprenorphine/naloxone. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
Total
n=23 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Race (NIH/OMB)
Black or African American
|
4 Participants
n=5 Participants
|
7 Participants
n=12 Participants
|
5 Participants
n=6 Participants
|
16 Participants
n=23 Participants
|
|
Race (NIH/OMB)
White
|
1 Participants
n=5 Participants
|
5 Participants
n=12 Participants
|
1 Participants
n=6 Participants
|
7 Participants
n=23 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=12 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=23 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=12 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=23 Participants
|
|
Blood Oxygen Saturation (SpO2)
|
98.2 percentage of oxygen saturation
STANDARD_DEVIATION 0.8 • n=5 Participants • The analysis population consisted of all participants who received at least 1 dose of IP during Run-in Period; Investigational Period and Down-titration Period.
|
97.8 percentage of oxygen saturation
STANDARD_DEVIATION 1.9 • n=11 Participants • The analysis population consisted of all participants who received at least 1 dose of IP during Run-in Period; Investigational Period and Down-titration Period.
|
97.8 percentage of oxygen saturation
STANDARD_DEVIATION 1.2 • n=6 Participants • The analysis population consisted of all participants who received at least 1 dose of IP during Run-in Period; Investigational Period and Down-titration Period.
|
97.9 percentage of oxygen saturation
STANDARD_DEVIATION 1.5 • n=22 Participants • The analysis population consisted of all participants who received at least 1 dose of IP during Run-in Period; Investigational Period and Down-titration Period.
|
|
End Tidal Carbon Dioxide (CO2)
|
40 millimeter of mercury (mmHg)
STANDARD_DEVIATION 0 • n=1 Participants • The analysis population consisted of all participants who received at least 1 dose of IP during Run-in Period; Investigational Period and Down-titration Period.
|
40.4 millimeter of mercury (mmHg)
STANDARD_DEVIATION 4.1 • n=12 Participants • The analysis population consisted of all participants who received at least 1 dose of IP during Run-in Period; Investigational Period and Down-titration Period.
|
38.2 millimeter of mercury (mmHg)
STANDARD_DEVIATION 5.1 • n=6 Participants • The analysis population consisted of all participants who received at least 1 dose of IP during Run-in Period; Investigational Period and Down-titration Period.
|
39.7 millimeter of mercury (mmHg)
STANDARD_DEVIATION 4.3 • n=19 Participants • The analysis population consisted of all participants who received at least 1 dose of IP during Run-in Period; Investigational Period and Down-titration Period.
|
|
Age, Continuous
|
41.4 Years
STANDARD_DEVIATION 5.2 • n=5 Participants
|
40.2 Years
STANDARD_DEVIATION 9.2 • n=12 Participants
|
43.2 Years
STANDARD_DEVIATION 10.3 • n=6 Participants
|
41.2 Years
STANDARD_DEVIATION 8.5 • n=23 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
3 Participants
n=12 Participants
|
2 Participants
n=6 Participants
|
7 Participants
n=23 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
9 Participants
n=12 Participants
|
4 Participants
n=6 Participants
|
16 Participants
n=23 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=12 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=23 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
5 Participants
n=5 Participants
|
12 Participants
n=12 Participants
|
6 Participants
n=6 Participants
|
23 Participants
n=23 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=12 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=23 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=12 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=23 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=12 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=23 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=12 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=23 Participants
|
PRIMARY outcome
Timeframe: From first dose of study drug up to end of study visit (up to day 27)Population: The analysis population was the Safety Analysis Set (SAF), which consisted of all participants who received at least 1 dose of ASP8062.
An AE is defined as any untoward medical occurrence in a participant administered an Investigational Product (IP) and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding; abnormal laboratory test result or other safety assessment, symptom, or disease temporally associated with the use of IP whether or not considered related to the IP. A treatment-emergent adverse event (TEAE) was defined as an AE with onset at any time from first dosing until last scheduled procedure. AEs were considered serious (SAEs) if the AE resulted in death, was life-threatening, resulted in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, resulted in congenital anomaly, or birth defect or required inpatient hospitalization or led to prolongation of hospitalization.
Outcome measures
| Measure |
Buprenorphine/Naloxone (Run-in Period)
n=23 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. Participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
n=12 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.
|
ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
n=12 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 19 through 26. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
n=6 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of Placebo concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.
|
Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
n=6 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 19 through 26. After randomization on day 12, participants received a single oral dose of Placebo concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
|---|---|---|---|---|---|
|
Number of Participants With Adverse Events (AEs)
TEAE
|
16 Participants
|
6 Participants
|
7 Participants
|
6 Participants
|
2 Participants
|
|
Number of Participants With Adverse Events (AEs)
Drug-Related TEAE
|
12 Participants
|
6 Participants
|
5 Participants
|
6 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events (AEs)
Serious TEAE
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events (AEs)
Drug-Related Serious TEAE
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events (AEs)
TEAE Leading to Death
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events (AEs)
Drug-Related TEAE Leading to Death
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events (AEs)
TEAE Leading to Withdrawal of Treatment
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events (AEs)
Drug-Related TEAE Leading to Withdrawal of Treatment
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events (AEs)
Death
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Up to day 27Population: The analysis population was the SAF, which consisted of all participants who received at least 1 dose of Investigational Product (IP).
The Columbia-Suicide Severity Rating Scale (C-SSRS) is a clinician administered assessment tool that evaluates suicidal ideation and behavior. Number of participants that have an affirmative response to the 5 items for suicidal ideation (1. Wish to be dead, 2. Non-specific active suicidal thoughts, 3. Active suicidal ideation with any methods (not plan) without intent to act, 4. Active suicidal ideation with some intent to act, without specific plan, 5. Active suicidal ideation with specific plan and intent) and/or to the 5 items for suicidal behavior (1. Preparatory acts or behavior, 2. Aborted attempt, 3. Interrupted attempt, 4. Actual attempt, 5. Completed suicide) were reported.
Outcome measures
| Measure |
Buprenorphine/Naloxone (Run-in Period)
n=23 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. Participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
n=12 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.
|
ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
n=12 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 19 through 26. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
n=6 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of Placebo concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.
|
Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
n=6 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 19 through 26. After randomization on day 12, participants received a single oral dose of Placebo concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
|---|---|---|---|---|---|
|
Number of Participants With Suicidal Ideation and/or Suicidal Behavior as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: 'buprenorphine/naloxone': Baseline and 1 hour postdose Day 11; 'ASP8062 in combination with buprenorphine/naloxone' and 'Placebo ASP8062 in combination with buprenorphine/naloxone': Baseline and 1 hour postdose Day 12Population: The analysis population was the SAF, which consisted of all participants who received at least 1 dose of IP and had baseline and post dose measures taken. It was pre-specified to assess only the Run-in Period and Investigational Period Arms/Groups for this Outcome Measure.
The blood oxygen saturation (SpO2 was measured using a pulse oximeter placed on the participant's fingertip. Change from baseline in SpO2 was calculated as Day 11 minus Baseline for arm 'buprenorphine/naloxone', and Day 12 minus Baseline for arms 'ASP8062 in combination with buprenorphine/naloxone' and 'Placebo ASP8062 in combination with buprenorphine/naloxone'. Baseline observation was last non-missing observation prior to first dose.
Outcome measures
| Measure |
Buprenorphine/Naloxone (Run-in Period)
n=18 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. Participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
n=11 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.
|
ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
n=6 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 19 through 26. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of Placebo concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.
|
Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
Participants received multiple sublingual doses of buprenorphine/naloxone on days 19 through 26. After randomization on day 12, participants received a single oral dose of Placebo concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
|---|---|---|---|---|---|
|
Change From Baseline in Blood Oxygen Saturation (SpO2) at Predose
|
0.2 Percentage of oxygen saturation
Standard Deviation 2.1
|
-0.4 Percentage of oxygen saturation
Standard Deviation 2.3
|
-0.3 Percentage of oxygen saturation
Standard Deviation 1.9
|
—
|
—
|
PRIMARY outcome
Timeframe: 'buprenorphine/naloxone': Baseline and 1 hour postdose Day 11; 'ASP8062 in combination with buprenorphine/naloxone' and 'Placebo ASP8062 in combination with buprenorphine/naloxone': Baseline and 1 hour postdose Day 12Population: The analysis population was the SAF, which consisted of all participants who received at least 1 dose of IP and had both baseline and post dose measures taken. It was pre-specified to assess only the Run-in Period and Investigational Period Arms/Groups for this Outcome Measure.
The blood oxygen saturation (SpO2) was measured using a pulse oximeter placed on the participant's fingertip. Change from baseline in SpO2 was calculated as Day 11 minus Baseline for arm 'buprenorphine/naloxone', and Day 12 minus Baseline for arms 'ASP8062 in combination with buprenorphine/naloxone' and 'Placebo ASP8062 in combination with buprenorphine/naloxone'. Baseline observation was last non-missing observation prior to first dose.
Outcome measures
| Measure |
Buprenorphine/Naloxone (Run-in Period)
n=18 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. Participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
n=11 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.
|
ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
n=6 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 19 through 26. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of Placebo concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.
|
Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
Participants received multiple sublingual doses of buprenorphine/naloxone on days 19 through 26. After randomization on day 12, participants received a single oral dose of Placebo concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
|---|---|---|---|---|---|
|
Change From Baseline in Blood Oxygen Saturation (SpO2) at 1 Hour Postdose
|
0.1 Percentage of oxygen saturation
Standard Deviation 2.5
|
-0.6 Percentage of oxygen saturation
Standard Deviation 2.6
|
-0.7 Percentage of oxygen saturation
Standard Deviation 2.3
|
—
|
—
|
PRIMARY outcome
Timeframe: 'buprenorphine/naloxone': Baseline and 2 hour postdose Day 11; 'ASP8062 in combination with buprenorphine/naloxone' and 'Placebo ASP8062 in combination with buprenorphine/naloxone': Baseline and 2 hour postdose Day 12Population: The analysis population was the SAF, which consisted of all participants who received at least 1 dose of IP and had both baseline and post dose measures taken. It was pre-specified to assess only the Run-in Period and Investigational Period Arms/Groups for this Outcome Measure.
The blood oxygen saturation (SpO2) was measured using a pulse oximeter placed on the participant's fingertip. Change from baseline in SpO2 was calculated as Day 11 minus Baseline for arm 'buprenorphine/naloxone', and Day 12 minus Baseline for arms 'ASP8062 in combination with buprenorphine/naloxone' and 'Placebo ASP8062 in combination with buprenorphine/naloxone'. Baseline observation was last non-missing observation prior to first dose.
Outcome measures
| Measure |
Buprenorphine/Naloxone (Run-in Period)
n=18 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. Participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
n=11 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.
|
ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
n=6 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 19 through 26. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of Placebo concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.
|
Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
Participants received multiple sublingual doses of buprenorphine/naloxone on days 19 through 26. After randomization on day 12, participants received a single oral dose of Placebo concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
|---|---|---|---|---|---|
|
Change From Baseline in Blood Oxygen Saturation (SpO2) at 2 Hour Postdose
|
0.2 Percentage of oxygen saturation
Standard Deviation 2.2
|
-0.8 Percentage of oxygen saturation
Standard Deviation 2.0
|
0.3 Percentage of oxygen saturation
Standard Deviation 1.8
|
—
|
—
|
PRIMARY outcome
Timeframe: 'buprenorphine/naloxone': Baseline and 4 hour postdose Day 11; 'ASP8062 in combination with buprenorphine/naloxone' and 'Placebo ASP8062 in combination with buprenorphine/naloxone': Baseline and 4 hour postdose Day 12Population: The analysis population was the SAF, which consisted of all participants who received at least 1 dose of IP and had both baseline and post dose measures taken. It was pre-specified to assess only the Run-in Period and Investigational Period Arms/Groups for this Outcome Measure.
The blood oxygen saturation (SpO2) was measured using a pulse oximeter placed on the participant's fingertip. Change from baseline in SpO2 was calculated as Day 11 minus Baseline for arm 'buprenorphine/naloxone', and Day 12 minus Baseline for arms 'ASP8062 in combination with buprenorphine/naloxone' and 'Placebo ASP8062 in combination with buprenorphine/naloxone'. Baseline observation was last non-missing observation prior to first dose.
Outcome measures
| Measure |
Buprenorphine/Naloxone (Run-in Period)
n=18 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. Participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
n=11 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.
|
ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
n=6 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 19 through 26. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of Placebo concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.
|
Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
Participants received multiple sublingual doses of buprenorphine/naloxone on days 19 through 26. After randomization on day 12, participants received a single oral dose of Placebo concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
|---|---|---|---|---|---|
|
Change From Baseline in Blood Oxygen Saturation (SpO2) at 4 Hour Postdose
|
0.3 Percentage of oxygen saturation
Standard Deviation 1.9
|
-0.4 Percentage of oxygen saturation
Standard Deviation 1.7
|
-0.2 Percentage of oxygen saturation
Standard Deviation 1.2
|
—
|
—
|
PRIMARY outcome
Timeframe: 'buprenorphine/naloxone': Baseline and 8 hour postdose Day 11; 'ASP8062 in combination with buprenorphine/naloxone' and 'Placebo ASP8062 in combination with buprenorphine/naloxone': Baseline and 8 hour postdose Day 12Population: The analysis population was the SAF, which consisted of all participants who received at least 1 dose of IP and had both baseline and post dose measures taken. It was pre-specified to assess only the Run-in Period and Investigational Period Arms/Groups for this Outcome Measure.
The blood oxygen saturation (SpO2) was measured using a pulse oximeter placed on the participant's fingertip. Change from baseline in SpO2 was calculated as Day 11 minus Baseline for arm 'buprenorphine/naloxone', and Day 12 minus Baseline for arms 'ASP8062 in combination with buprenorphine/naloxone' and 'Placebo ASP8062 in combination with buprenorphine/naloxone'. Baseline observation was last non-missing observation prior to first dose.
Outcome measures
| Measure |
Buprenorphine/Naloxone (Run-in Period)
n=18 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. Participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
n=11 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.
|
ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
n=6 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 19 through 26. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of Placebo concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.
|
Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
Participants received multiple sublingual doses of buprenorphine/naloxone on days 19 through 26. After randomization on day 12, participants received a single oral dose of Placebo concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
|---|---|---|---|---|---|
|
Change From Baseline in Blood Oxygen Saturation (SpO2) at 8 Hour Postdose
|
0.1 Percentage of oxygen saturation
Standard Deviation 2.3
|
-0.1 Percentage of oxygen saturation
Standard Deviation 2.4
|
0.7 Percentage of oxygen saturation
Standard Deviation 1.6
|
—
|
—
|
PRIMARY outcome
Timeframe: 'buprenorphine/naloxone': Baseline and 12 hour postdose Day 11; 'ASP8062 in combination with buprenorphine/naloxone' and 'Placebo ASP8062 in combination with buprenorphine/naloxone': Baseline and 12 hour postdose Day 12Population: The analysis population was the SAF, which consisted of all participants who received at least 1 dose of IP and had both baseline and post dose measures taken. It was pre-specified to assess only the Run-in Period and Investigational Period Arms/Groups for this Outcome Measure.
The blood oxygen saturation (SpO2) was measured using a pulse oximeter placed on the participant's fingertip. Change from baseline in SpO2 was calculated as Day 11 minus Baseline for arm 'buprenorphine/naloxone', and Day 12 minus Baseline for arms 'ASP8062 in combination with buprenorphine/naloxone' and 'Placebo ASP8062 in combination with buprenorphine/naloxone'. Baseline observation was last non-missing observation prior to first dose.
Outcome measures
| Measure |
Buprenorphine/Naloxone (Run-in Period)
n=18 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. Participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
n=11 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.
|
ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
n=6 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 19 through 26. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of Placebo concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.
|
Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
Participants received multiple sublingual doses of buprenorphine/naloxone on days 19 through 26. After randomization on day 12, participants received a single oral dose of Placebo concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
|---|---|---|---|---|---|
|
Change From Baseline in Blood Oxygen Saturation (SpO2) at 12 Hour Postdose
|
-0.6 Percentage of oxygen saturation
Standard Deviation 1.8
|
-0.3 Percentage of oxygen saturation
Standard Deviation 2.5
|
-0.5 Percentage of oxygen saturation
Standard Deviation 0.8
|
—
|
—
|
PRIMARY outcome
Timeframe: 'ASP8062 in combination with buprenorphine/naloxone' and 'Placebo ASP8062 in combination with buprenorphine/naloxone': Baseline and predose Day 12Population: The analysis population was the Safety Analysis Set (SAF), which consisted of all participants who received at least 1 dose of ASP8062. It was pre-specified to assess only the Investigational Period Arms/Groups for this Outcome Measure.
End tidal CO2 measurements was obtained per participant utilizing a portable bedside capnography device. Change from baseline in CO2 was calculated as Day 12 minus Baseline for arms 'ASP8062 in combination with buprenorphine/naloxone' and 'Placebo ASP8062 in combination with buprenorphine/naloxone'.
Outcome measures
| Measure |
Buprenorphine/Naloxone (Run-in Period)
n=12 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. Participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
n=6 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.
|
ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
Participants received multiple sublingual doses of buprenorphine/naloxone on days 19 through 26. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of Placebo concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.
|
Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
Participants received multiple sublingual doses of buprenorphine/naloxone on days 19 through 26. After randomization on day 12, participants received a single oral dose of Placebo concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
|---|---|---|---|---|---|
|
Change From Baseline in End Tidal Carbon Dioxide (CO2) at Predose
|
-1.3 mmHg
Standard Deviation 4.0
|
0.5 mmHg
Standard Deviation 6.1
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: 'buprenorphine/naloxone': Baseline and 1 hour postdose Day 11; 'ASP8062 in combination with buprenorphine/naloxone' and 'Placebo ASP8062 in combination with buprenorphine/naloxone': Baseline and 1 hour postdose Day 12Population: The analysis population was the SAF, which consisted of all participants who received at least 1 dose of IP and had both baseline and post dose measures taken. It was pre-specified to assess only the Run-in Period and Investigational Period Arms/Groups for this Outcome Measure.
End tidal CO2 measurements was obtained per participant utilizing a portable bedside capnography device. Change from baseline in CO2 was calculated as Day 11 minus Baseline for arm 'buprenorphine/naloxone', and Day 12 minus Baseline for arms 'ASP8062 in combination with buprenorphine/naloxone' and 'Placebo ASP8062 in combination with buprenorphine/naloxone'.
Outcome measures
| Measure |
Buprenorphine/Naloxone (Run-in Period)
n=19 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. Participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
n=12 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.
|
ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
n=6 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 19 through 26. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of Placebo concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.
|
Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
Participants received multiple sublingual doses of buprenorphine/naloxone on days 19 through 26. After randomization on day 12, participants received a single oral dose of Placebo concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
|---|---|---|---|---|---|
|
Change From Baseline in End Tidal Carbon Dioxide (CO2) at 1 Hour Postdose
|
1.3 mmHg
Standard Deviation 5.8
|
-0.5 mmHg
Standard Deviation 4.0
|
3.7 mmHg
Standard Deviation 7.2
|
—
|
—
|
PRIMARY outcome
Timeframe: 'buprenorphine/naloxone': Baseline and 2 hour postdose Day 11; 'ASP8062 in combination with buprenorphine/naloxone' and 'Placebo ASP8062 in combination with buprenorphine/naloxone': Baseline and 2 hour postdose Day 12Population: The analysis population was the SAF, which consisted of all participants who received at least 1 dose of IP and had both baseline and post dose measures taken. It was pre-specified to assess only the Run-in Period and Investigational Period Arms/Groups for this Outcome Measure.
End tidal CO2 measurements was obtained per participant utilizing a portable bedside capnography device. Change from baseline in CO2 was calculated as Day 11 minus Baseline for arm 'buprenorphine/naloxone', and Day 12 minus Baseline for arms 'ASP8062 in combination with buprenorphine/naloxone' and 'Placebo ASP8062 in combination with buprenorphine/naloxone'.
Outcome measures
| Measure |
Buprenorphine/Naloxone (Run-in Period)
n=19 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. Participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
n=12 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.
|
ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
n=6 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 19 through 26. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of Placebo concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.
|
Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
Participants received multiple sublingual doses of buprenorphine/naloxone on days 19 through 26. After randomization on day 12, participants received a single oral dose of Placebo concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
|---|---|---|---|---|---|
|
Change From Baseline in End Tidal Carbon Dioxide (CO2) at 2 Hour Postdose
|
1.2 mmHg
Standard Deviation 5.1
|
0.3 mmHg
Standard Deviation 3.2
|
4.2 mmHg
Standard Deviation 5.0
|
—
|
—
|
PRIMARY outcome
Timeframe: 'buprenorphine/naloxone': Baseline and 4 hour postdose Day 11; 'ASP8062 in combination with buprenorphine/naloxone' and 'Placebo ASP8062 in combination with buprenorphine/naloxone': Baseline and 4 hour postdose Day 12Population: The analysis population was the SAF, which consisted of all participants who received at least 1 dose of IP and had both baseline and post dose measures taken. It was pre-specified to assess only the Run-in Period and Investigational Period Arms/Groups for this Outcome Measure.
End tidal CO2 measurements was obtained per participant utilizing a portable bedside capnography device. Change from baseline in CO2 was calculated as Day 11 minus Baseline for arm 'buprenorphine/naloxone', and Day 12 minus Baseline for arms 'ASP8062 in combination with buprenorphine/naloxone' and 'Placebo ASP8062 in combination with buprenorphine/naloxone'.
Outcome measures
| Measure |
Buprenorphine/Naloxone (Run-in Period)
n=18 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. Participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
n=12 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.
|
ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
n=6 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 19 through 26. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of Placebo concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.
|
Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
Participants received multiple sublingual doses of buprenorphine/naloxone on days 19 through 26. After randomization on day 12, participants received a single oral dose of Placebo concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
|---|---|---|---|---|---|
|
Change From Baseline in End Tidal Carbon Dioxide (CO2) at 4 Hour Postdose
|
0.9 mmHg
Standard Deviation 4.9
|
-1.0 mmHg
Standard Deviation 2.3
|
5.3 mmHg
Standard Deviation 7.9
|
—
|
—
|
PRIMARY outcome
Timeframe: 'buprenorphine/naloxone': Baseline and 8 hour postdose Day 11; 'ASP8062 in combination with buprenorphine/naloxone' and 'Placebo ASP8062 in combination with buprenorphine/naloxone': Baseline and 8 hour postdose Day 12Population: The analysis population was the SAF, which consisted of all participants who received at least 1 dose of IP and had both baseline and post dose measures taken. It was pre-specified to assess only the Run-in Period and Investigational Period Arms/Groups for this Outcome Measure.
End tidal CO2 measurements was obtained per participant utilizing a portable bedside capnography device. Change from baseline in CO2 was calculated as Day 11 minus Baseline for arm 'buprenorphine/naloxone', and Day 12 minus Baseline for arms 'ASP8062 in combination with buprenorphine/naloxone' and 'Placebo ASP8062 in combination with buprenorphine/naloxone'.
Outcome measures
| Measure |
Buprenorphine/Naloxone (Run-in Period)
n=18 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. Participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
n=12 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.
|
ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
n=6 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 19 through 26. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of Placebo concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.
|
Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
Participants received multiple sublingual doses of buprenorphine/naloxone on days 19 through 26. After randomization on day 12, participants received a single oral dose of Placebo concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
|---|---|---|---|---|---|
|
Change From Baseline in End Tidal Carbon Dioxide (CO2) at 8 Hour Postdose
|
3.1 mmHg
Standard Deviation 4.1
|
1.4 mmHg
Standard Deviation 1.9
|
6.0 mmHg
Standard Deviation 5.7
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose on day 12 and at the following postdose time points on day 12: 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144, 168, 216 and 264 hour(s)Population: The analysis population was the Pharmacokinetic Analysis Set (PKAS), which consisted of all participants who received at least 1 dose of ASP8062 for which concentration data was available to facilitate derivation of at least 1 primary pharmacokinetic parameter.
AUCinf was recorded from the PK plasma samples collected. Samples for AUCinf were collected for arm 'ASP8062 in combination with buprenorphine/naloxone' at Day 12.
Outcome measures
| Measure |
Buprenorphine/Naloxone (Run-in Period)
n=12 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. Participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.
|
ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
Participants received multiple sublingual doses of buprenorphine/naloxone on days 19 through 26. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of Placebo concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.
|
Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
Participants received multiple sublingual doses of buprenorphine/naloxone on days 19 through 26. After randomization on day 12, participants received a single oral dose of Placebo concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
|---|---|---|---|---|---|
|
Pharmacokinetics (PK) of ASP8062 in Plasma: Area Under the Concentration-time Curve From the Time of Dosing Extrapolated to Time Infinity (AUCinf)
|
4450 h*ng/mL
Standard Deviation 1750
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose on day 12 and at the following postdose time points on day 12: 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144, 168, 216 and 264 hour(s)Population: The analysis population was the PKAS, which consisted of all participants who received at least 1 dose of ASP8062 for which concentration data was available to facilitate derivation of at least 1 primary pharmacokinetic parameter.
AUClast was recorded from the PK plasma samples collected. Samples for AUClast were collected for arm 'ASP8062 in combination with buprenorphine/naloxone' at Day 12.
Outcome measures
| Measure |
Buprenorphine/Naloxone (Run-in Period)
n=12 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. Participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.
|
ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
Participants received multiple sublingual doses of buprenorphine/naloxone on days 19 through 26. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of Placebo concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.
|
Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
Participants received multiple sublingual doses of buprenorphine/naloxone on days 19 through 26. After randomization on day 12, participants received a single oral dose of Placebo concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
|---|---|---|---|---|---|
|
Pharmacokinetics (PK) of ASP8062 in Plasma: Area Under the Concentration-time Curve From the Time of Dosing to the Last Measurable Concentration (AUClast)
|
4270 h*ng/mL
Standard Deviation 1620
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose on day 12 and at the following postdose time points on day 12: 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144, 168, 216 and 264 hour(s)Population: The analysis population was the PKAS, which consisted of all participants who received at least 1 dose of ASP8062 for which concentration data was available to facilitate derivation of at least 1 primary pharmacokinetic parameter.
Cmax was recorded from the PK plasma samples collected. Samples for Cmax were collected for arm 'ASP8062 in combination with buprenorphine/naloxone' at Day 12.
Outcome measures
| Measure |
Buprenorphine/Naloxone (Run-in Period)
n=12 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. Participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.
|
ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
Participants received multiple sublingual doses of buprenorphine/naloxone on days 19 through 26. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of Placebo concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.
|
Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
Participants received multiple sublingual doses of buprenorphine/naloxone on days 19 through 26. After randomization on day 12, participants received a single oral dose of Placebo concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
|---|---|---|---|---|---|
|
Pharmacokinetics (PK) of ASP8062 in Plasma: Maximum Concentration (Cmax)
|
152 ng/mL
Standard Deviation 36.7
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose on day 11 and at the following postdose time points on day 11: 0.25, 0.5, 1, 1.5, 2, 3, 4, 8, 12 and 16 hour(s)Population: The analysis population was the PKAS, which consisted of all participants who received at least 1 dose of buprenorphine (in any applicable period) and for which concentration data were available to facilitate derivation of at least 1 primary pharmacokinetic parameter.
AUC24 was recorded from the PK plasma samples collected. Samples for AUC24 were collected for arm 'buprenorphine/naloxone' at Day 11; 'ASP8062 in combination with buprenorphine/naloxone' and 'ASP8062 in combination with Placebo' at Day 12.
Outcome measures
| Measure |
Buprenorphine/Naloxone (Run-in Period)
n=15 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. Participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
n=12 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.
|
ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
n=6 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 19 through 26. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of Placebo concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.
|
Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
Participants received multiple sublingual doses of buprenorphine/naloxone on days 19 through 26. After randomization on day 12, participants received a single oral dose of Placebo concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
|---|---|---|---|---|---|
|
Pharmacokinetics (PK) of Buprenorphine in Plasma: Area Under the Concentration-time Curve From the Time of Dosing to 24 Hours (AUC24)
|
63800 h*pg/mL
Standard Deviation 20300
|
53500 h*pg/mL
Standard Deviation 18300
|
67700 h*pg/mL
Standard Deviation 18700
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose on day 11 and at the following postdose time points on day 11: 0.25, 0.5, 1, 1.5, 2, 3, 4, 8, 12 and 16 hour(s)Population: The analysis population was the PKAS, which consisted of all participants who received at least 1 dose of buprenorphine (in any applicable period) and for which concentration data were available to facilitate derivation of at least 1 primary pharmacokinetic parameter.
Cmax was recorded from the PK plasma samples collected. Samples for Cmax were collected for arm 'buprenorphine/naloxone' at Day 11; 'ASP8062 in combination with buprenorphine/naloxone' and 'ASP8062 in combination with Placebo' at Day 12.
Outcome measures
| Measure |
Buprenorphine/Naloxone (Run-in Period)
n=18 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. Participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
n=12 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.
|
ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
n=6 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 19 through 26. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of Placebo concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.
|
Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
Participants received multiple sublingual doses of buprenorphine/naloxone on days 19 through 26. After randomization on day 12, participants received a single oral dose of Placebo concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
|---|---|---|---|---|---|
|
Pharmacokinetics (PK) of Buprenorphine in Plasma: Cmax
|
7790 pg/mL
Standard Deviation 3280
|
6790 pg/mL
Standard Deviation 3230
|
8440 pg/mL
Standard Deviation 2200
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose on day 11 and at the following postdose time points on day 11: 0.25, 0.5, 1, 1.5, 2, 3, 4, 8, 12 and 16 hour(s)Population: The analysis population was the PKAS, which consisted of all participants who received at least 1 dose of buprenorphine (in any applicable period) and for which concentration data were available to facilitate derivation of at least 1 primary pharmacokinetic parameter.
AUC24 was recorded from the PK plasma samples collected. Samples for AUC24 were collected for arm 'buprenorphine/naloxone' at Day 11; 'ASP8062 in combination with buprenorphine/naloxone' and 'ASP8062 in combination with Placebo' at Day 12.
Outcome measures
| Measure |
Buprenorphine/Naloxone (Run-in Period)
n=15 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. Participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
n=12 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.
|
ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
n=6 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 19 through 26. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of Placebo concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.
|
Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
Participants received multiple sublingual doses of buprenorphine/naloxone on days 19 through 26. After randomization on day 12, participants received a single oral dose of Placebo concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
|---|---|---|---|---|---|
|
Pharmacokinetics (PK) of Norbuprenorphine (Buprenorphine's Metabolite) in Plasma: AUC24
|
97600 h*pg/mL
Standard Deviation 49200
|
96200 h*pg/mL
Standard Deviation 45700
|
104000 h*pg/mL
Standard Deviation 43600
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose on day 11 and at the following postdose time points on day 11: 0.25, 0.5, 1, 1.5, 2, 3, 4, 8, 12 and 16 hour(s)Population: The analysis population was the PKAS, which consisted of all participants who received at least 1 dose of buprenorphine (in any applicable period) and for which concentration data were available to facilitate derivation of at least 1 primary pharmacokinetic parameter.
Cmax was recorded from the PK plasma samples collected. Samples for Cmax were collected for arm 'buprenorphine/naloxone' at Day 11; 'ASP8062 in combination with buprenorphine/naloxone' and 'ASP8062 in combination with Placebo' at Day 12.
Outcome measures
| Measure |
Buprenorphine/Naloxone (Run-in Period)
n=18 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. Participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
n=12 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.
|
ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
n=6 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 19 through 26. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of Placebo concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.
|
Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
Participants received multiple sublingual doses of buprenorphine/naloxone on days 19 through 26. After randomization on day 12, participants received a single oral dose of Placebo concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
|---|---|---|---|---|---|
|
Pharmacokinetics (PK) of Norbuprenorphine (Buprenorphine's Metabolite) in Plasma: Cmax
|
5260 pg/mL
Standard Deviation 2350
|
6060 pg/mL
Standard Deviation 2870
|
5730 pg/mL
Standard Deviation 1930
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose on day 12 and at the following postdose time points on day 12: 0.25, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 16, 24, 168, 216 and 264 hour(s)Population: The analysis population was the PKAS, which consisted of all participants who received at least 1 dose of naloxone (in any applicable period) and for which concentration data were available to facilitate derivation of at least 1 primary pharmacokinetic parameter.
AUC24 was recorded from the PK plasma samples collected. Samples for AUC24 were collected for arm 'buprenorphine/naloxone' at Day 11; 'ASP8062 in combination with buprenorphine/naloxone' and 'ASP8062 in combination with Placebo' at Day 12.
Outcome measures
| Measure |
Buprenorphine/Naloxone (Run-in Period)
n=16 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. Participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
n=12 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.
|
ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
n=6 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 19 through 26. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of Placebo concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.
|
Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
Participants received multiple sublingual doses of buprenorphine/naloxone on days 19 through 26. After randomization on day 12, participants received a single oral dose of Placebo concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
|---|---|---|---|---|---|
|
Pharmacokinetics (PK) of Naloxone in Plasma: AUC24
|
1270 h*pg/mL
Standard Deviation 656
|
1060 h*pg/mL
Standard Deviation 624
|
1090 h*pg/mL
Standard Deviation 379
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose on day 12 and at the following postdose time points on day 12: 0.25, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 16, 24, 168, 216 and 264 hour(s)Population: The analysis population was the PKAS, which consisted of all participants who received at least 1 dose of naloxone (in any applicable period) and for which concentration data were available to facilitate derivation of at least 1 primary pharmacokinetic parameter.
Cmax was recorded from the PK plasma samples collected. Samples for Cmax were collected for arm 'buprenorphine/naloxone' at Day 11; 'ASP8062 in combination with buprenorphine/naloxone' and 'ASP8062 in combination with Placebo' at Day 12.
Outcome measures
| Measure |
Buprenorphine/Naloxone (Run-in Period)
n=18 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. Participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
n=12 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.
|
ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
n=6 Participants
Participants received multiple sublingual doses of buprenorphine/naloxone on days 19 through 26. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of Placebo concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.
|
Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
Participants received multiple sublingual doses of buprenorphine/naloxone on days 19 through 26. After randomization on day 12, participants received a single oral dose of Placebo concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
|---|---|---|---|---|---|
|
Pharmacokinetics (PK) of Naloxone in Plasma: Cmax
|
464 pg/mL
Standard Deviation 355
|
382 pg/mL
Standard Deviation 284
|
363 pg/mL
Standard Deviation 160
|
—
|
—
|
Adverse Events
Buprenorphine/Naloxone
Serious events: 0 serious events
Other events: 16 other events
Deaths: 0 deaths
ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Buprenorphine/Naloxone
n=23 participants at risk
Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. Participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
n=12 participants at risk
Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.
|
ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
n=12 participants at risk
Participants received multiple sublingual doses of buprenorphine/naloxone on days 19 through 26. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
n=6 participants at risk
Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of Placebo concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.
|
Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
n=6 participants at risk
Participants received multiple sublingual doses of buprenorphine/naloxone on days 19 through 26. After randomization on day 12, participants received a single oral dose of Placebo concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
|
|---|---|---|---|---|---|
|
Gastrointestinal disorders
Constipation
|
17.4%
4/23 • Number of events 4 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/12 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/12 • From first dose of study drug up to end of study visit (up to day 27)
|
33.3%
2/6 • Number of events 2 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/6 • From first dose of study drug up to end of study visit (up to day 27)
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/23 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/12 • From first dose of study drug up to end of study visit (up to day 27)
|
8.3%
1/12 • Number of events 1 • From first dose of study drug up to end of study visit (up to day 27)
|
16.7%
1/6 • Number of events 1 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/6 • From first dose of study drug up to end of study visit (up to day 27)
|
|
Gastrointestinal disorders
Nausea
|
4.3%
1/23 • Number of events 1 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/12 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/12 • From first dose of study drug up to end of study visit (up to day 27)
|
16.7%
1/6 • Number of events 1 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/6 • From first dose of study drug up to end of study visit (up to day 27)
|
|
Gastrointestinal disorders
Salivary hypersecretion
|
0.00%
0/23 • From first dose of study drug up to end of study visit (up to day 27)
|
8.3%
1/12 • Number of events 1 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/12 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/6 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/6 • From first dose of study drug up to end of study visit (up to day 27)
|
|
Gastrointestinal disorders
Vomiting
|
4.3%
1/23 • Number of events 1 • From first dose of study drug up to end of study visit (up to day 27)
|
8.3%
1/12 • Number of events 1 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/12 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/6 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/6 • From first dose of study drug up to end of study visit (up to day 27)
|
|
General disorders
Asthenia
|
0.00%
0/23 • From first dose of study drug up to end of study visit (up to day 27)
|
8.3%
1/12 • Number of events 1 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/12 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/6 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/6 • From first dose of study drug up to end of study visit (up to day 27)
|
|
General disorders
Drug withdrawal syndrome
|
0.00%
0/23 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/12 • From first dose of study drug up to end of study visit (up to day 27)
|
25.0%
3/12 • Number of events 3 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/6 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/6 • From first dose of study drug up to end of study visit (up to day 27)
|
|
General disorders
Feeling of relaxation
|
0.00%
0/23 • From first dose of study drug up to end of study visit (up to day 27)
|
8.3%
1/12 • Number of events 1 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/12 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/6 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/6 • From first dose of study drug up to end of study visit (up to day 27)
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
17.4%
4/23 • Number of events 4 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/12 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/12 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/6 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/6 • From first dose of study drug up to end of study visit (up to day 27)
|
|
Musculoskeletal and connective tissue disorders
Muscle twitching
|
0.00%
0/23 • From first dose of study drug up to end of study visit (up to day 27)
|
8.3%
1/12 • Number of events 1 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/12 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/6 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/6 • From first dose of study drug up to end of study visit (up to day 27)
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
8.7%
2/23 • Number of events 2 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/12 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/12 • From first dose of study drug up to end of study visit (up to day 27)
|
16.7%
1/6 • Number of events 1 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/6 • From first dose of study drug up to end of study visit (up to day 27)
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
8.7%
2/23 • Number of events 2 • From first dose of study drug up to end of study visit (up to day 27)
|
8.3%
1/12 • Number of events 1 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/12 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/6 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/6 • From first dose of study drug up to end of study visit (up to day 27)
|
|
Nervous system disorders
Dizziness
|
0.00%
0/23 • From first dose of study drug up to end of study visit (up to day 27)
|
8.3%
1/12 • Number of events 1 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/12 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/6 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/6 • From first dose of study drug up to end of study visit (up to day 27)
|
|
Nervous system disorders
Headache
|
34.8%
8/23 • Number of events 13 • From first dose of study drug up to end of study visit (up to day 27)
|
33.3%
4/12 • Number of events 5 • From first dose of study drug up to end of study visit (up to day 27)
|
16.7%
2/12 • Number of events 3 • From first dose of study drug up to end of study visit (up to day 27)
|
50.0%
3/6 • Number of events 4 • From first dose of study drug up to end of study visit (up to day 27)
|
33.3%
2/6 • Number of events 4 • From first dose of study drug up to end of study visit (up to day 27)
|
|
Nervous system disorders
Somnolence
|
4.3%
1/23 • Number of events 1 • From first dose of study drug up to end of study visit (up to day 27)
|
8.3%
1/12 • Number of events 1 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/12 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/6 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/6 • From first dose of study drug up to end of study visit (up to day 27)
|
|
Psychiatric disorders
Anxiety
|
13.0%
3/23 • Number of events 3 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/12 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/12 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/6 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/6 • From first dose of study drug up to end of study visit (up to day 27)
|
|
Psychiatric disorders
Insomnia
|
21.7%
5/23 • Number of events 6 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/12 • From first dose of study drug up to end of study visit (up to day 27)
|
8.3%
1/12 • Number of events 1 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/6 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/6 • From first dose of study drug up to end of study visit (up to day 27)
|
|
Psychiatric disorders
Nervousness
|
0.00%
0/23 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/12 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/12 • From first dose of study drug up to end of study visit (up to day 27)
|
16.7%
1/6 • Number of events 1 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/6 • From first dose of study drug up to end of study visit (up to day 27)
|
|
Renal and urinary disorders
Dysuria
|
0.00%
0/23 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/12 • From first dose of study drug up to end of study visit (up to day 27)
|
8.3%
1/12 • Number of events 1 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/6 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/6 • From first dose of study drug up to end of study visit (up to day 27)
|
|
Renal and urinary disorders
Pollakiuria
|
0.00%
0/23 • From first dose of study drug up to end of study visit (up to day 27)
|
8.3%
1/12 • Number of events 1 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/12 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/6 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/6 • From first dose of study drug up to end of study visit (up to day 27)
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/23 • From first dose of study drug up to end of study visit (up to day 27)
|
8.3%
1/12 • Number of events 1 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/12 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/6 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/6 • From first dose of study drug up to end of study visit (up to day 27)
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/23 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/12 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/12 • From first dose of study drug up to end of study visit (up to day 27)
|
16.7%
1/6 • Number of events 1 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/6 • From first dose of study drug up to end of study visit (up to day 27)
|
|
Vascular disorders
Phlebitis
|
0.00%
0/23 • From first dose of study drug up to end of study visit (up to day 27)
|
8.3%
1/12 • Number of events 1 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/12 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/6 • From first dose of study drug up to end of study visit (up to day 27)
|
0.00%
0/6 • From first dose of study drug up to end of study visit (up to day 27)
|
Additional Information
Clinical Trial Disclosure
Astellas Pharma Global Development, Inc.
Phone: 800-888-7704
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Institute and/or Principal Investigator may publish trial data generated at their specific study site after Sponsor publication of the multi-center data. Sponsor must receive a site's manuscript prior to publication for review and comment as specified in the Investigator Agreement.
- Publication restrictions are in place
Restriction type: OTHER