Phase 2
Completed N=124
Multiple Dose Pharmacokinetics Depot Buprenorphine in Opioid-Dependent Subjects
Opioid Related Disorder
Source: ClinicalTrials.gov NCT01738503 ↗
Enrolled (actual)
124
Serious AEs
4.8%
Results posted
Jan 2018
Primary outcomePrimary: Participants With Treatment-Emergent Adverse Events (TEAEs) — 24; 15; 15; 15 Participants
Summary
This is an open-label study in treatment seeking opioid-dependent subjects for safety, tolerability, pharmacokinetics (PK), efficacy markers, and opioid receptor availability of subcutaneous injections of depot buprenorphine after induction and stabilization of treatment seeking subjects onto Subutex.
Subjects were planned to receive 4 subcutaneous (SC) injections of RBP-6000 separated by 28 days (Cohorts 1-5) or 6 SC injections of RBP-6000 separated by 28 days (Cohort 6) after a 13-day induction and dose stabilisation period on SUBUTEX Sublingual (SL) tablet at dose levels of 8-24 mg.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Participants With Treatment-Emergent Adverse Events (TEAEs) |
24; 15; 15; 15; 15; 15 | — |
| PRIMARY Buprenorphine PK: % Fluctuation |
256.993; 272.702; 233.978; 268.690; 227.874; 245.513 | — |
| PRIMARY Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC) |
28.452; 40.971; 63.019; 30.029; 46.681; 46.628 | — |
| PRIMARY Buprenorphine PK: Average Plasma Concentration (Cavg) |
1.186; 1.707; 2.626; 1.251; 1.945; 1.943 | — |
| PRIMARY Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax) |
3.521; 5.350; 7.571; 3.964; 5.260; 5.813 | — |
| PRIMARY Buprenorphine PK: Minimum Observed Plasma Concentration (Cmin) |
0.524; 0.806; 1.385; 0.568; 0.920; 0.927 | — |
| PRIMARY Buprenorphine PK: Swing of Plasma Concentrations |
656.884; 665.742; 493.475; 597.543; 500.322; 534.280 | — |
| PRIMARY Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax) |
2.000; 1.017; 1.117; 2.000; 2.000; 2.000 | — |
| PRIMARY Buprenorphine PK: Accumulation Index in Terms of Area Under the Curve (Rac(AUC)) |
2.580; 2.738; 3.456; 3.379; 2.837; 3.573 | — |
| PRIMARY Buprenorphine PK: Accumulation Index in Terms of Maximum Observed Plasma Drug Concentration (Rac(Cmax)) |
1.380; 1.560; 1.766; 1.729; 1.559; 1.908 | — |
| PRIMARY Buprenorphine PK: Apparent Clearance at Steady-State (CLss/F) Following Injections 4 and 6 |
85.543; 85.043; 105.155; 87.404; 105.390; 80.860 | — |
| PRIMARY Buprenorphine PK: Area Under Plasma Concentration Time Curve From Time Zero Of Injection 4 (AUC0-∞) |
2280.295; 3521.376 | — |
| PRIMARY Buprenorphine PK: Terminal Phase Half Life (t1/2) Calculated For Injection 4 |
550.329; 138.238 | — |
| PRIMARY Norbuprenorphine PK: % Fluctuation |
69.798; 94.132; 79.225; 82.834; 89.832; 71.213 | — |
| PRIMARY Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC) |
42.536; 72.339; 134.739; 49.312; 65.558; 98.407 | — |
| PRIMARY Norbuprenorphine PK: Average Plasma Concentration (Cavg) |
1.772; 3.014; 5.614; 2.055; 2.732; 4.100 | — |
| PRIMARY Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax) |
2.559; 4.941; 8.515; 3.268; 5.268; 5.820 | — |
| PRIMARY Norbuprenorphine PK: Minimum Observed Plasma Concentration (Cmin) |
1.361; 2.342; 4.287; 1.582; 2.482; 2.923 | — |
| PRIMARY Norbuprenorphine PK: Swing of Plasma Concentrations |
93.472; 130.823; 102.059; 109.416; 124.601; 101.558 | — |
| PRIMARY Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax) |
2.000; 1.017; 1.000; 2.000; 2.000; 2.000 | — |
| PRIMARY Norbuprenorphine PK: Accumulation Index in Terms of Area Under the Curve (Rac(AUC)) |
1.071; 1.924; 1.147; 1.709; 1.711; 1.247 | — |
| PRIMARY Norbuprenorphine PK: Accumulation Index in Terms of Maximum Observed Plasma Drug Concentration (Rac(Cmax)) |
0.300; 0.697; 0.272; 0.548; 0.445; 0.730 | — |
| PRIMARY Norbuprenorphine PK: Area Under Plasma Concentration Time Curve From Time Zero Of Injection 4 and 6 (AUC0-∞) |
499.733; 1583.219; 639.892; 1472.769; 737.097 | — |
| PRIMARY Norbuprenorphine PK: Terminal Phase Half Life (t1/2) Calculated For Injection 4 |
405.325; 241.914; 334.080; 310.879; 158.840 | — |
| SECONDARY Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Prior to Injections 1, 2, 3, 4 and 6 |
17.6; 17.7; 20.4; 16.2; 17.9; 16.7 | — |
| SECONDARY Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Prior to Injections 1, 2, 3, 4 and 6 |
40.2; 47.8; 45.1; 42.7; 42.1; 43.9 | — |
| SECONDARY Change From Baseline in the Clinical Opioid Craving Visual Analog Scale (VAS) Total Score Prior to Injections 1, 2, 3, 4 and 6 |
85.6; 89.7; 87.2; 86.0; 85.1; 87.4 | — |
| SECONDARY Change From Baseline in the Clinical Global Impression Severity (CGI-S) Scale on Days 1, 7, 29, 57, 85 and 141 |
4.3; 4.3; 4.4; 4.6; 4.7; 4.6 | — |
| SECONDARY Change From Baseline in the Clinical Global Impression Improvement (CGI-I) Scale on Days 7, 29, 57, 85 and 141 |
4.0; 4.1; 4.0; 4.0; 4.0; 4.0 | — |
| SECONDARY Columbia Suicide Severity Rating Scale (C-SSRS): Severity |
1.0; 1.8; 2.0; 1.0; 1.3; 1.0 | — |
| SECONDARY Percentage of Urine Drug Screen Samples Negative for Opioids |
41.2; 42.0; 54.6; 49.9; 41.6; 64.9 | — |
Eligibility Criteria
Inclusion Criteria
- Male and female subjects
- Agree not to take any buprenorphine products other than those administered for the current study throughout participation in the study
- Body mass index (BMI) of >18.0 to 450 msec in males and QTcF > 470 in females at screening
- Abuse of buprenorphine or use of buprenorphine within 14 days of informed consent
Data sourced from ClinicalTrials.gov (NCT01738503). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.