Buprenorphine

Drug information

Delivery device(s)

No delivery device

Scale-up prospects

In 2022, 830,000 doses were manufactured

Tentative equipment list for manufacturing

Not provided

Manufacturing

• Manufacturing and distribution of Camurus’ products is based on a multi-stage supply chain with several participants involved. Braeburn Pharmaceuticals overlooks the manufacturing of the FDA approved drugs of FluidCrystal in liaison with a third party manufacturer. • The manufacturing process includes: - weighing, dissolving, sterile filtration, filling, closing, visual inspection, labelling, assembly in safety device and secondary packaging. The manufacturing process setup aims to reduce product manufacturing waste by 20% and to increase the use of packaging material originating from susta

Specific analytical instrument required for characterization of formulation

The listed analytical instrument used was HPLC with UV detection

HS-14-499

Identifier

NCT02672111

Link

https://clinicaltrials.gov/study/NCT02672111

Phase

Phase III

Status

Completed

Sponsor

Braeburn Pharmaceuticals

More details

Open-label multi-center, 48 week safety study, consistent with standard practice for long-term safety studies. This one year safety study will utilize CAM2038 q1w (once weekly) and q4w (once monthly) and will have 3 phases: Screening, Treatment, and Follow-up.

Purpose

Long-Term Safety Study of Buprenorphine (CAM2038) in Adult Outpatients With Opioid Use Disorder

Interventions

Intervention 1

Intervention 2

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2015-11-01

Anticipated Date of Last Follow-up
2020-04-29

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2017-05-01

Actual Completion Date
2017-05-01

Studied populations

Age Cohort

• Adults
• Older Adults

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
No

Comments about the studied populations

Inclusion Criteria: 1. Subject must provide written informed consent prior to the conduct of any study-related procedures. 2. Male or female, 18-65 years of age, inclusive. 3. Female subjects of childbearing potential must be willing to use a highly effective method of contraception during the entire study (Screening Visit to Follow-Up Visit). 4. Current diagnosis of moderate or severe opioid use disorder (DSM-V) or past medical history of opioid use disorder currently being treated with SL BPN. 5. Considered by the Investigator to be a good candidate for BPN treatment, based on medical and psychosocial history. 6. Subjects must meet one of the following criteria for BPN treatment history: * Voluntarily seeking treatment for opioid use disorder (not currently on BPN treatment for at l

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

228

Allocation

Not provided

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Open label

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key resources

HS-15-549

Identifier

NCT02710526

Link

https://clinicaltrials.gov/study/NCT02710526

Phase

Phase II

Status

Completed

Sponsor

Braeburn Pharmaceuticals

More details

Phase II, open label, partially randomized, three treatment group study designed to evaluate the steady state pharmacokinetics of buprenorphine and norbuprenorphine following repeated subcutaneous administrations of CAM2038.

Purpose

Phase II Pharmacokinetics Study of CAM2038

Interventions

Intervention 1

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2015-02-01

Anticipated Date of Last Follow-up
2020-04-29

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2017-05-17

Actual Completion Date
2017-07-03

Studied populations

Age Cohort

• Adults
• Older Adults

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
No

Comments about the studied populations

Inclusion Criteria: 1. Subject must provide written informed consent prior to the conduct of any study related procedures. 2. Male or non pregnant, non lactating female subject, aged 19 to 65 years, inclusive. 3. Body mass index between 19 and 35 kg/m2, inclusive. 4. Current diagnosis of moderate to severe opioid use disorder (according to the DSM 5) or past medical history of opioid use disorder currently being treated with SL BPN. 5. Subject must be taking SL BPN (Subutex® equivalent) 24 mg (Group 1 and Group 2) or ≥24 mg (Group 3) daily for at least 30 days prior to Screening. 6. Subject has a history of moderate to severe chronic non cancer pain. 7. Male and female subjects of childbearing potential must be willing to use a reliable method of contraception during the entire study (Scr

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

66

Allocation

Randomized

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Open label

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key resources

HS-11-421

Identifier

NCT02651584

Link

https://clinicaltrials.gov/study/NCT02651584

Phase

Phase III

Status

Completed

Sponsor

Braeburn Pharmaceuticals

More details

Phase III, randomized, double-blind, double-dummy, active-controlled, parallel group multi-center trial, designed to evaluate the non-inferiority of CAM2038 compared to an existing standard of care (SL BPN/NX) in initiation and maintenance treatment with BPN.

Purpose

Clinical Trial of CAM2038, Long-acting Subcutaneous Buprenorphine Injections for Treatment of Patients With Opioid Dependence

Interventions

Intervention 1

Intervention 2

Intervention 3

Intervention 4

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2015-12-01

Anticipated Date of Last Follow-up
2019-08-06

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2016-10-01

Actual Completion Date
2016-11-01

Studied populations

Age Cohort

• Adults
• Older Adults

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
No

Comments about the studied populations

Inclusion Criteria: 1. Subject must provide written informed consent prior to the conduct of any trial-related procedures. 2. Male or female, 18-65 years of age, inclusive. 3. Diagnosis of moderate or severe opioid use disorder as described (DSM-V). 4. Voluntarily seeking treatment for opioid use disorder. 5. Have not received medication-assisted treatment for opioid use disorder within 60 days prior to randomization. 6. Considered by the Investigator to be a good candidate for BPN treatment, based on medical and psychosocial history. 7. Male or Female subjects of childbearing potential must be willing to use a reliable method of contraception during the entire trial (Screening visit to Follow-up visit) Exclusion Criteria: 1. Current diagnosis of Acquired Immune Deficiency Syndrome (AID

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

428

Allocation

Randomized

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Double-blind masking

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key resources

CAM2038

Identifier

NCT02946073

Link

https://clinicaltrials.gov/study/NCT02946073

Phase

Phase III

Status

Completed

Sponsor

Braeburn Pharmaceuticals

More details

This is a Phase III, placebo-controlled, multicenter study with an enriched-enrollment withdrawal (EEW) design to evaluate the efficacy and safety of CAM2038 in opioid-experienced subjects with moderate to severe CLBP that requires continuous, around-the-clock (ATC) opioid treatment ≥ 40 mg morphine equivalent dose (MED). The study includes 5 phases: A Screening Phase (up to 2 weeks), a Transition Phase (up to 2 weeks), an Open-Label Titration Phase (up to 10 weeks), a Double-Blind Treatment Phase including a Final Study Visit (12 weeks), and a Follow-up Phase (4 weeks). The overall duration of participation in the core phase of the study (randomized Double-Blind Phase) is up to 30 weeks, from the Screening Phase through the Follow-up Phase. Subjects who complete the Double-Blind Treatment

Purpose

Buprenorphine (CAM2038) in Subjects With a Recent History of Moderate to Severe Chronic Low Back Pain

Interventions

Intervention 1

Intervention 2

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2016-09-01

Anticipated Date of Last Follow-up
2021-09-20

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2018-05-01

Actual Completion Date
2019-02-01

Studied populations

Age Cohort

• Adults
• Older Adults

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
No

Comments about the studied populations

Inclusion Criteria: 1. Written informed consent provided prior to the conduct of any study-related procedures. 2. Male or non-pregnant, non-lactating female subject, greater than or equal to 18 years old. 3. Body mass index (BMI) between 18 and 38 kg/m2, inclusive. 4. Treated with daily opioids for moderate to severe CLBP for a minimum of 3 months prior to Screening. 5. On a stable dose of ≥40 mg/day of oral morphine or MED during the 14 days prior to Screening. 6. Systolic blood pressure ≥100 mmHg and diastolic blood pressure ≥60 mmHg. 7. Female subject of childbearing potential who is willing to use a reliable method of contraception during the entire study (Screening Visit to final Follow-up). To be considered not of childbearing potential, female subjects must be surgically sterile (h

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

1053

Allocation

Randomized

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Quadruple-blind masking

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key resources

Proprietary excipients used

No proprietary excipient used

Novel excipients or existing excipients at a concentration above Inactive Ingredients Database (IID) for the specified route of administration

• Glycerol dioleate (a lipid) • Ethanol (as solvent) • Phospholipids

Residual solvents used

No residual solvent used

Description

Robust controlled-release formulations

Brief description

Not provided

Representative patent

EP2787975B1

Category

Not provided

Patent holder

Camurus AB

Exclusivity

Not provided

Expiration date

November 28, 2032

Status

Active

Description

Opioid formulations

Brief description

A depot precursor formulation comprising: a) a controlled-release matrix; b) at least oxygen containing organic solvent; c) at least 12% by weigh of at least one active agent selected from buprenorphine and salts thereof, calculated as buprenorphine free base. Corresponding depot compositions and methods of treatment in pain management, by opioid maintenance and related methods are provided.

Representative patent

US20210137916A1

Category

Not provided

Patent holder

Camurus AB

Exclusivity

Not provided

Expiration date

July 26, 2032

Status

Active

Publications

Vorspan, F., Hjelmström, P., Simon, N., Benyamina, A., Dervaux, A., Brousse, G., Jamain, T., Kosim, M., & Rolland, B. (2019). What place for prolonged-release buprenorphine depot-formulation Buvidal® in the treatment arsenal of opioid dependence? Insights from the French experience on buprenorphine. Expert opinion on drug delivery, 16(9), 907–914. https://doi.org/10.1080/17425247.2019.1649252

Abstract

Introduction: Since the 1990s, opioid maintenance treatments (OMTs), i.e. mostly methadone and buprenorphine, have represented the therapeutic cornerstone of opioid dependence. In France, the public health strategy on opioid dependence, identified here as the 'French model', has consisted of offering a facilitated access to buprenorphine, to reach a large treatment coverage and reduce opioid-related mortality. Areas covered: Recently, a new formulation of subcutaneous buprenorphine depot (Buvidal®) has been approved in Europe for treatment of opioid dependence. The place of Buvidal® among the pre-existing arsenal of OMTs is discussed in the light of the pharmacological specificities of this new formulation, and with the particular standpoint of the French model on opioid dependence. Expert opinion: Buvidal® could constitute a promising treatment option mainly in case of: 1) OMT initiation, including in non-specialized addiction medicine care; 2) Discharge from prison or hospital; Diversion/misuse of 3) buprenorphine or 4) methadone; 5) Clinically stabilized patients wishing to avoid daily oral taking of the medication. As such, this new formulation should be highly accessible, which will require specific pathways through care as the product is intended to be administered by a healthcare professional.

Nunes, E. V., Comer, S. D., Lofwall, M. R., Walsh, S. L., Peterson, S., Tiberg, F., Hjelmstrom, P., & Budilovsky-Kelley, N. R. (2024). Extended-Release Injection vs Sublingual Buprenorphine for Opioid Use Disorder With Fentanyl Use: A Post Hoc Analysis of a Randomized Clinical Trial. JAMA network open, 7(6), e2417377. https://doi.org/10.1001/jamanetworkopen.2024.17377

Importance: Fentanyl has exacerbated the opioid use disorder (OUD) and opioid overdose epidemic. Data on the effectiveness of medications for OUD among patients using fentanyl are limited.

Objective: To assess the effectiveness of sublingual or extended-release injection formulations of buprenorphine for the treatment of OUD among patients with and without fentanyl use.

Design, setting, and participants: Post hoc analysis of a 24-week, randomized, double-blind clinical trial conducted at 35 outpatient sites in the US from December 2015 to November 2016 of sublingual buprenorphine-naloxone vs extended-release subcutaneous injection buprenorphine (CAM2038) for patients with OUD subgrouped by presence vs absence of fentanyl or norfentanyl in urine at baseline. Study visits with urine testing occurred weekly for 12 weeks, then 6 times between weeks 13 and 24. Data were analyzed on an intention-to-treat basis from March 2022 to August 2023.

Intervention: Weekly and monthly subcutaneous buprenorphine vs daily sublingual buprenorphine-naloxone.

Main outcomes and measures: Retention in treatment, percentage of urine samples negative for any opioids (missing values imputed as positive), percentage of urine samples negative for fentanyl or norfentanyl (missing values not imputed), and scores on opiate withdrawal scales and visual analog craving scales.

Results: Of 428 participants, 123 (subcutaneous buprenorphine, n = 64; sublingual buprenorphine-naloxone, n = 59; mean [SD] age, 39.1 [10.8] years; 75 men [61.0%]) had evidence of baseline fentanyl use and 305 (subcutaneous buprenorphine, n = 149; buprenorphine-naloxone, n = 156; mean [SD] age, 38.1 [11.1] years; 188 men [61.6%]) did not have evidence of baseline fentanyl use. Study completion was similar between the fentanyl-positive (60.2% [74 of 123]) and fentanyl-negative (56.7% [173 of 305]) subgroups. The mean percentage of urine samples negative for any opioid were 28.5% among those receiving subcutaneous buprenorphine and 18.8% among those receiving buprenorphine-naloxone in the fentanyl-positive subgroup (difference, 9.6%; 95% CI, -3.0% to 22.3%) and 36.7% among those receiving subcutaneous buprenorphine and 30.6% among those receiving buprenorphine-naloxone in the fentanyl-negative subgroup (difference, 6.1%; 95% CI, -1.9% to 14.1%), with significant main associations of baseline fentanyl status and treatment group. In the fentanyl-positive subgroup, the mean percentage of urine samples negative for fentanyl during the study was 74.6% among those receiving subcutaneous buprenorphine vs 61.9% among those receiving sublingual buprenorphine-naloxone (difference, 12.7%; 95% CI, 9.6%-15.9%). Opioid withdrawal and craving scores decreased rapidly after treatment initiation across all groups.

Conclusions and relevance: In this post hoc analysis of a randomized clinical trial of sublingual vs extended-release injection buprenorphine for OUD, buprenorphine appeared to be effective among patients with baseline fentanyl use. Patients with fentanyl use had fewer opioid-negative urine samples during the trial compared with the fentanyl-negative subgroup. These findings suggest that the subcutaneous buprenorphine formulation may be more effective at reducing fentanyl use.

Trial registration: ClinicalTrials.gov Identifier: NCT02651584.

Additional documents

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Useful links

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