A Multiple Dose Opioid Challenge Study

• Sponsor: Braeburn Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02611752
• Collaborator: (none)
• Enrollment: 47
• Locations: 3
• Arms: 2
• Duration (Months): 6
• Patients Per Site: 15.7
• Patients Per Site Per Month: 2.6

Study Details

Study Description

Brief Summary

Multi-site, randomized, double-blind, repeat-dose Phase 2 study to evaluate the degree and duration of action of multiple doses of CAM2038 in blocking the effects of hydromorphone in patients with moderate or severe opioid use disorder.

Condition or Disease	Intervention/Treatment	Phase
Moderate or Severe Opioid Use Disorder	Drug: CAM2038	Phase 2

Detailed Description

This is a multi-site, randomized, double-blind, repeat-dose Phase 2 study to evaluate the degree and duration of action of multiple doses of CAM2038 q1w in blocking the effects of a mu opioid agonist (hydromorphone) in patients with moderate or severe opioid use disorder. The study will involve 4 phases: Screening, Qualification, Treatment, and Follow-up.

The study will enroll a sufficient number of subjects to ensure that at least 48 subjects complete the study (24 subjects per group with at least 16 females in total). Replacement subjects may be added at the discretion of the sponsor with the agreement of the investigator.

Study Design

• Study Type: Interventional
• Actual Enrollment: 47 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multiple Dose Opioid Challenge Study to Assess Blockade of Subjective Opioid Effects of CAM2038 q1w (Buprenorphine FluidCrystal® Subcutaneous Injection Depots) In Adults With Opioid Use Disorder
• Study Start Date: Oct 1, 2015
• Actual Primary Completion Date: Apr 1, 2016
• Actual Study Completion Date: Apr 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CAM2038 q1w, 24 mg CAM2038 q1w 24 mg will be administered on Day 0 and Day 7. Hydromorphone 0 mg (placebo), 6 mg and 18 mg will be subsequently administered during 4 challenge sessions on Days 1-3, 4-6, 8-10 and 11-13	Drug: CAM2038; CAM2038 subcutaneous injection
Experimental: CAM2038 q1w, 32 mg CAM2038 q1w 32 mg will be administered on Day 0 and Day 7. Hydromorphone 0 mg (placebo), 6 mg and 18 mg will be subsequently administered during 4 challenge sessions on Days 1-3, 4-6, 8-10 and 11-13	Drug: CAM2038; CAM2038 subcutaneous injection

Outcome Measures

Primary Outcome Measures

1. Treatment Phase Drug Liking Visual Analog Scale (VAS) Emax Scores for Baseline and Four Challenge Sessions Compared to Baseline (Completer Population) for CAM2038 q1w, 24 mg [17 days]

   Treatment Phase Drug Liking Visual Analog Scale (VAS) item "At this moment, my liking of this drug is" for Baseline and Four Challenge sessions Compared to Baseline (Completer Population) for CAM2038 q1w, 24 mg, where values can range from 0 (strong disliking) to 100 (strong liking) and 50 is the neutral point. Higher scores mean worse outcome.

2. Treatment Phase Drug Liking Visual Analog Scale (VAS) Maximum Effect (Emax) Scores for Baseline and Four Challenge Sessions Compared to Baseline (Completer Population) for CAM2038 q1w, 32 mg [17 days]

   Treatment Phase Drug Liking Visual Analog Scale (VAS) item "At this moment, my liking of this drug is" for Baseline and Four Challenge sessions Compared to Baseline (Completer Population), where values can range from 0 (strong disliking) to 100 (strong liking) and 50 is the neutral point. Higher scores mean worse outcome.

3. Inferential Analysis Results Drug Liking Visual Analog Scale (VAS) for Maximum Effect (Emax) Scores for Qualification/Baseline and Four Challenge Sessions (Completer Population) for CAM2038 q1w, 24 mg [17 days]

   Inferential Analysis Results Drug Liking Visual Analog Scale (VAS) item "At this moment, my liking of this drug is" for Qualification/Baseline and Four Challenge sessions (Completer Population) for CAM2038 q1w, 24 mg, where values can range from 0 (strong disliking) to 100 (strong liking) and 50 is the neutral point. Higher scores mean worse outcome.

4. Inferential Analysis Results Drug Liking Visual Analog Scale (VAS) Maximum Effect (Emax) Scores for Qualification/Baseline and Four Challenge Sessions (Completer Population) for CAM2038 q1w, 32 mg [17 days]

   Inferential Analysis Results Drug Liking Visual Analog Scale (VAS) item "At this moment, my liking of this drug is" for Qualification/Baseline and Four Challenge sessions (Completer Population) for CAM2038 q1w, 32 mg, where values can range from 0 (strong disliking) to 100 (strong liking) and 50 is the neutral point. Higher scores mean worse outcome.

Secondary Outcome Measures

1. Inferential Analysis Results for Unipolar High Visual Analog Scale (VAS) for Maximum Effect (Emax) (Completer Population) [15 days]

   Inferential Analysis Results for Unipolar High Visual Analog Scale (VAS) for Maximum Effect (Emax) (Completer Population) comparing hydromorphone challenge doses in each of the baseline and four challenge sequence with each other, presented as Least Squares (LS) Mean with Standard Error (SE) and 95% Confidence Interval (CI). VAS item "At this moment, I feel high" where values can range from 0 (Not at all High) to 100 (Extremely High).

2. Inferential Analysis Results for Unipolar Good Drug Effects Visual Analog Scale (VAS) for Maximum Effect (Emax) (Completer Population) [15 days]

   Inferential Analysis Results for Unipolar Good Drug Effects Visual Analog Scale (VAS) for Maximum Effect (Emax) (Completer Population) comparing hydromorphone challenge doses in each of the baseling and four challenge sequences with each other, presented as Least Squares (LS) Mean with Standard Error (SE) and 95% Confidence Interval (CI). VAS item "At this moment, I feel good drug effects" where values can range from 0 (Not at all ) to 100 (Extremely).

3. Analysis of Treatment Phase Unipolar Bad Drug Effects Visual Analog Scale (VAS) for Maximum Effect (Emax) in 24 mg CAM2038 q1w Group (Completer Population) [15 days]

   Analysis of Treatment Phase Unipolar Bad Drug Effects Visual Analog Scale (VAS) for Maximum Effect (Emax) in 24 mg CAM2038 q1w group (Completer Population) , presented as Least Squares (LS) mean with Standard Error (SE) for all 3 doses of hydromorphone in baseline and 4 Challenge Sessions. VAS item "At this moment, I feel bad effects" where values can range from 0 (Not at all) to 100 (Extremely).

4. Analysis of Treatment Phase Unipolar Bad Drug Effects Visual Analog Scale (VAS) for Maximum Effect (Emax) in 32 mg CAM2038 q1w Group (Completer Population) [15 days]

   Analysis of Treatment Phase Unipolar Bad Drug Effects Visual Analog Scale (VAS) for Maximum Effect (Emax) in 32 mg CAM2038 q1w group (Completer Population) , presented as Least Squares (LS) mean with Standard Error (SE) for all 3 doses of hydromorphone in baseline and 4 Challenge Sessions. VAS item "At this moment, I feel bad effects" where values can range from 0 (Not at all) to 100 (Extremely).

5. Analysis Results for Unipolar Desire to Use Visual Analog Scale (VAS) for Maximum Effect (Emax) (Completer Population) [15 days]

   Analysis Results for Desire to Use Visual Analog Scale (VAS) for Maximum Effect (Emax) (Completer Population) comparing hydromorphone challenge doses in each of the baseline and four challenge sequence with each other, presented as Least Squares (LS) Mean with Standard Error (SE) and 95% Confidence Interval (CI). VAS item "At this moment, I desire opiods" where values can range from 0 (Definitely not) to 100 (Definitely so).

6. Analysis Results for Bipolar Alertness/Drowsiness Visual Analog Scale (VAS) for Maximum Effect (Emax) (Completer Population) [15 days]

   Analysis Results for Bipolar Alertness/Drowsiness Visual Analog Scale (VAS) for Maximum Effect (Emax) (Completer Population) presented as Least Squares (LS) mean with Standard Error (SE) for all 3 doses of hydromorphone in baseline and 4 Challenge Sessions. VAS item "At this moment, my mental state is" where values can range from 0 (Very Drowsy) to 100 (Very alert), with 50 being neutral (Neither drowsy nor alert).

7. Analysis Results for Unipolar Any Drug Effects Visual Analog Scale (VAS) for Maximum Effect (Emax) (Completer Population) [15 days]

   Analysis Results for Unipolar Any Drug Effects Visual Analog Scale (VAS) for Maximum Effect (Emax) (Completer Population) presented as Least Squares (LS) mean with Standard Error (SE) for all 3 doses of hydromorphone in baseline and 4 Challenge Sessions. VAS item "At this moment, I fell any drug effects" where values can range from 0 (Not at all) to 100 (Extremely).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Patient had to provide written informed consent prior to the conduct of any study-related procedures.

2. Male or female, 18-55 years of age, inclusive.

3. Patients with a diagnosis of moderate or severe opioid use disorder (DSM-V) who were physically dependent on intravenous (IV) or insufflated opioids, and who were willing to undergo short-term BPN treatment.

4. Self-reported opioid-use of a minimum of 21 days in the 30 days prior to Screening.

5. Positive UDS for opioids at Screening or at check-in. If UDS was not positive, patients had to present with physical signs of withdrawal, as determined by the Investigator. The Investigator may have administered a naloxone challenge, in order to confirm opioid dependence at the Investigator's discretion.

6. Female patients of childbearing potential had to be willing to use a reliable method of contraception during the entire study (Screening Visit to Follow-up Phone Call).

7. Female patients of non-childbearing potential were surgically sterile (i.e., had undergone complete hysterectomy, bilateral oophorectomy, or tubal ligation) or in a menopausal state (at least 1 year without menses), as confirmed by follicle stimulating hormone (FSH) levels.

8. Male patients with female partners of childbearing potential had to agree to use a reliable method of contraception from Screening Visit through at least 3 months after the last dose of study drug. Male patients also must have agreed not to donate sperm during the study through at least 3 months after the last dose of study drug.

9. Were willing and able to comply with the study requirements (including blood sampling), complete study assessments, visit the clinic, and remain confined in the CRU for up to 25 consecutive days.

Exclusion Criteria:

1. History or presence of any clinically significant psychiatric, endocrine, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, renal, or other major disease or illness at Screening, which in the opinion of the Investigator would have jeopardized the safety of the patient or the validity of the study results.

2. Opioid-dependent patients who were actively seeking treatment for their moderate to severe opioid use disorder.

3. Patients with positive UDS for BPN, barbiturates, or methadone or breath alcohol on the day of check-in to the CRU.

4. Aspartate aminotransferase (AST) levels >3 X the upper limit of normal, alanine aminotransferase (ALT) levels >3 X the upper limit of normal, total bilirubin >1.5 X the upper limit of normal, or creatinine >1.5 X the upper limit of normal on the Screening laboratory assessments and at inpatient check-in, or other clinically significant laboratory abnormalities, which in the opinion of the Investigator may have prevented the patient from safely participating in study.

5. Any clinically significant abnormality on the basis of medical history, vital signs, physical examination, 12-lead electrocardiogram ([ECG], QTcF ≥450 msec for males or ≥470 msec for females), and laboratory evaluation (including hematology, clinical chemistry, urinalysis, and serology [optional]) at Screening, in the opinion of the Investigator.

6. Significant symptoms, medical conditions, or other circumstances which, in the opinion of the Investigator, would have precluded compliance with the protocol, adequate cooperation in the study or obtaining informed consent, or may have prevented the patient from safely participating in study (including, but not limited to, the risks described as precautions, warnings, and contraindications in the current version of the Investigator's Brochure for CAM2038).

7. Patients were carefully screened to exclude individuals presenting with a clinically significant history of seizure disorders, history of asthma or other respiratory disorders, head injury, hypertension, or personal history of cardiovascular disease or clinically significant ECG abnormalities.

8. Current diagnosis of Acquired Immune Deficiency Syndrome.

9. Current diagnosis of chronic pain requiring opioids for treatment.

10. Patients who met the criteria for a diagnosis of moderate or severe substance use disorder according to DSM-V criteria for any other substances other than opioids, caffeine, or tobacco.

11. Pregnant or lactating, or planned to become pregnant during the study.

12. Clinically significant history of or current evidence of suicidal ideation or active suicidal behavior as based on the Columbia-Suicide Severity Rating Scale (C-SSRS; grade 4 or 5).

13. Hypersensitivity or allergy to BPN or other opioids or excipients of CAM2038.

14. Intolerance to venipuncture and/or difficulty with venous access, as per the judgment of the Investigator/research staff.

15. Patient was using an investigational drug or monoamine oxidase inhibitor or had used such within the last 30 days (or 5 times the half-life of the drug, if known and longer) prior to first drug administration in the Qualification Phase (i.e., IR morphine sulfate).

16. Required current use of agents that were strong inhibitors or inducers of cytochrome P450 3A4 (CYP3A4), such as some azole antifungals (e.g., ketoconazole), macrolide antibiotics (e.g., clarithromycin), or protease inhibitors (e.g., ritonavir, indinavir, and saquinavir).

17. If the patient was currently on probation or had any pending legal action that could have prohibited participation or compliance in the study.

18. A patient who, in the opinion of the Investigator, was considered unsuitable or unlikely to comply with the study protocol for any reason.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Vince and Associates Clinical Research	Overland Park	Kansas	United States	66212
2	University of Kentucky	Lexington	Kentucky	United States	40513
3	New York Psychiatric Institute	New York	New York	United States	10032

Sponsors and Collaborators

• Braeburn Pharmaceuticals

Investigators

• Principal Investigator: Sharon Walsh, PhD, University of Kentucky

Study Documents (Full-Text)

• Study Protocol - Nov 17, 2015
• Statistical Analysis Plan - Jun 13, 2016

More Information

Publications

None provided.

• Responsible Party: Braeburn Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02611752
• Other Study ID Numbers: HS-13-478
• First Posted: Nov 23, 2015
• Last Update Posted: Nov 14, 2019
• Last Verified: Aug 1, 2018

• Additional relevant MeSH terms: Opioid-Related Disorders; Buprenorphine

Study Results

Participant Flow

Arm/Group Title	CAM2038 q1w, 24 mg	CAM2038 q1w, 32 mg
Arm/Group Description	CAM2038 once weekly 24 mg subcutaneous injection will be administered on Day 0 and Day 7. Hydromorphone 0 mg (placebo), 6 mg and 18 mg intramuscular injection will be subsequently administered during 4 challenge sessions on Days 1-3, 4-6, 8-10 and 11-13	CAM2038 once weekly 32 mg subcutaneous injection will be administered on Day 0 and Day 7. Hydromorphone 0 mg (placebo), 6 mg and 18 mg intramuscular injection will be subsequently administered during 4 challenge sessions on Days 1-3, 4-6, 8-10 and 11-13
Period Title: Overall Study
STARTED	22	25
Day 1-3 Hydromorphone Challenge Injs	22	25
Day 4-6 Hydromorphone Challenge Injs	22	24
Day 8-10 Hydromorphone Challenge Injs	22	24
Day11-13 Hydromorphone Challenge Injs	22	24
COMPLETED	22	24
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	CAM2038 q1w, 24 mg	CAM2038 q1w, 32 mg	Total
Arm/Group Description	CAM2038 q1w 24 mg will be administered by subcutaneous injection on Day 0 and Day 7. Hydromorphone 0 mg (placebo) intramuscular injection will be administered on one day of the 3 days during 4 challenge sessions on Days 1-3, 4-6, 8-10 and 11-13.	CAM2038 q1w 32 mg will be administered by subcutaneous injection on Day 0 and Day 7. Hydromorphone 0 mg (placebo) intramuscular injection will be administered on one day of the 3 days during 4 challenge sessions on Days 1-3, 4-6, 8-10 and 11-13.	Total of all reporting groups
Overall Participants	22	25	47
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	36.1 (9.3)	35.6 (9.1)	35.8 (9.1)
Sex: Female, Male (Count of Participants)
Female	6 27.3%	6 24%	12 25.5%
Male	16 72.7%	19 76%	35 74.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	1 4%	1 2.1%
Not Hispanic or Latino	22 100%	24 96%	46 97.9%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	9 40.9%	15 60%	24 51.1%
White	12 54.5%	10 40%	22 46.8%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 4.5%	0 0%	1 2.1%
BMI, kg/m^2 (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	25.2 (4.28)	24.4 (4.25)	24.8 (4.24)

Outcome Measures

1. Primary Outcome

Title	Treatment Phase Drug Liking Visual Analog Scale (VAS) Emax Scores for Baseline and Four Challenge Sessions Compared to Baseline (Completer Population) for CAM2038 q1w, 24 mg
Description	Treatment Phase Drug Liking Visual Analog Scale (VAS) item "At this moment, my liking of this drug is" for Baseline and Four Challenge sessions Compared to Baseline (Completer Population) for CAM2038 q1w, 24 mg, where values can range from 0 (strong disliking) to 100 (strong liking) and 50 is the neutral point. Higher scores mean worse outcome.
Time Frame	17 days

Outcome Measure Data

Analysis Population Description

Mean Drug Liking VAS Scores over Time for CAM2038 q1w 24 mg by Hydromorphone Challenge Session, Completer Population (N=22)

Arm/Group Title	CAM2038 q1w, 24 mg - Hydromorphone 0 mg	CAM2038 q1w, 24 mg - Hydromorphone 6 mg	CAM2038 q1w, 24 mg - Hydromorphone 18 mg
Arm/Group Description	CAM2038 q1w 24 mg will be administered by subcutaneous injection on Day 0 and Day 7. Hydromorphone 0 mg (placebo) intramuscular injection will be administered on one day of the 3 days during baseline and 4 challenge sessions on Days -3--1, 1-3, 4-6, 8-10 and 11-13.	CAM2038 q1w 24 mg will be administered by subcutaneous injection on Day 0 and Day 7. Hydromorphone 6 mg intramuscular injection will be administered on one day of the 3 days during baseline and 4 challenge sessions on Days -3--1, 1-3, 4-6, 8-10 and 11-13.	CAM2038 q1w 24 mg will be administered by subcutaneous injection on Day 0 and Day 7. Hydromorphone 18 mg intramuscular injection will be administered on one day of the 3 days during baseline and 4 challenge sessions on Days -3--1, 1-3, 4-6, 8-10 and 11-13.
Measure Participants	22	22	22
Baseline	50.6 (1.48)	83.2 (1.48)	92.7 (1.48)
Days 1-3	51.3 (0.84)	52.2 (0.84)	53.1 (0.84)
Days 4-6	50.8 (0.84)	52.1 (0.84)	58.3 (0.84)
Days 8 -10	51.1 (0.84)	52.6 (0.84)	52.9 (0.84)
Days 11-13	51.0 (0.84)	51.9 (0.84)	54.6 (0.84)

2. Primary Outcome

Title	Treatment Phase Drug Liking Visual Analog Scale (VAS) Maximum Effect (Emax) Scores for Baseline and Four Challenge Sessions Compared to Baseline (Completer Population) for CAM2038 q1w, 32 mg
Description	Treatment Phase Drug Liking Visual Analog Scale (VAS) item "At this moment, my liking of this drug is" for Baseline and Four Challenge sessions Compared to Baseline (Completer Population), where values can range from 0 (strong disliking) to 100 (strong liking) and 50 is the neutral point. Higher scores mean worse outcome.
Time Frame	17 days

Outcome Measure Data

Analysis Population Description

Mean Drug Liking VAS Scores over Time for CAM2038 q1w 32 mg by Hydromorphone Challenge Session, Completer Population (N=24)

Arm/Group Title	CAM2038 q1w, 32 mg - Hydromorphone 0 mg	CAM2038 q1w, 32 mg - Hydromorphone 6 mg	CAM2038 q1w, 32 mg - Hydromorphone 18 mg
Arm/Group Description	CAM2038 q1w 32 mg will be administered by subcutaneous injection on Day 0 and Day 7. Hydromorphone 0 mg (placebo) intramuscular injection will be administered on one day of the 3 days during baseline and 4 challenge sessions on Days -3--1, 1-3, 4-6, 8-10 and 11-13.	CAM2038 q1w 32 mg will be administered by subcutaneous injection on Day 0 and Day 7. Hydromorphone 6 mg intramuscular injection will be administered on one day of the 3 days during baseline and 4 challenge sessions on Days -3--1, 1-3, 4-6, 8-10 and 11-13.	CAM2038 q1w 32 mg will be administered by subcutaneous injection on Day 0 and Day 7. Hydromorphone 18 mg intramuscular injection will be administered on one day of the 3 days during baseline and 4 challenge sessions on Days -3--1, 1-3, 4-6, 8-10 and 11-13.
Measure Participants	24	24	24
Baseline	52.9 (1.70)	79.6 (1.70)	93.2 (1.70)
Days 1-3	51.6 (1.01)	52.5 (1.01)	54.0 (1.01)
Days 4-6	51.5 (1.01)	53.0 (1.01)	56.0 (1.01)
Days 8 -10	51.7 (1.01)	52.3 (1.01)	54.2 (1.01)
Days 11-13	51.2 (1.01)	52.1 (1.01)	54.8 (1.01)

3. Primary Outcome

Title	Inferential Analysis Results Drug Liking Visual Analog Scale (VAS) for Maximum Effect (Emax) Scores for Qualification/Baseline and Four Challenge Sessions (Completer Population) for CAM2038 q1w, 24 mg
Description	Inferential Analysis Results Drug Liking Visual Analog Scale (VAS) item "At this moment, my liking of this drug is" for Qualification/Baseline and Four Challenge sessions (Completer Population) for CAM2038 q1w, 24 mg, where values can range from 0 (strong disliking) to 100 (strong liking) and 50 is the neutral point. Higher scores mean worse outcome.
Time Frame	17 days

Outcome Measure Data

Analysis Population Description

Mean Drug Liking VAS Scores over Time for CAM2038 q1w 24 mg by Hydromorphone Challenge Session, Completer Population (N=22)

Arm/Group Title	CAM2038 q1w, 24 mg - Hydromorphone 6 Mg-Hydromorphone 0 mg	CAM2038 q1w, 24 mg - Hydromorphone 18 mg- Hydromorphone 0mg	CAM2038 q1w, 24 mg - Hydromorphone 18 mg- Hydromorphone 6 mg
Arm/Group Description	CAM2038 q1w 24 mg will be administered by subcutaneous injection on Day 0 and Day 7. Hydromorphone 0 mg (placebo) and 6 mg intramuscular injection will be administered on 2 of the 3 days during baseline and 4 challenge sessions on Days -3--1, 1-3, 4-6, 8-10 and 11-13.	CAM2038 q1w 24 mg will be administered by subcutaneous injection on Day 0 and Day 7. Hydromorphone 18 mg and Hydromorphone 0 mg intramuscular injection will be administered on 2 of the 3 days during baseline and 4 challenge sessions on Days -3--1,1-3, 4-6, 8-10 and 11-13.	CAM2038 q1w 24 mg will be administered by subcutaneous injection on Day 0 and Day 7. Hydromorphone 18 mg and Hydromorphone 6 mg intramuscular injection will be administered on 2 of the 3 days during baseline and 4 challenge sessions on Days -3--1,1-3, 4-6, 8-10 and 11-13.
Measure Participants	22	22	22
Qualification/Baseline	32.7 (1.90)	42.1 (1.90)	9.5 (1.90)
Days 1-3	0.9 (1.12)	1.8 (1.12)	0.9 (1.12)
Days 4-6	1.3 (1.12)	7.4 (1.12)	6.2 (1.12)
Days 8 -10	1.5 (1.12)	1.8 (1.12)	0.3 (1.12)
Days 11-13	0.9 (1.12)	3.6 (1.12)	2.7 (1.12)

4. Primary Outcome

Title	Inferential Analysis Results Drug Liking Visual Analog Scale (VAS) Maximum Effect (Emax) Scores for Qualification/Baseline and Four Challenge Sessions (Completer Population) for CAM2038 q1w, 32 mg
Description	Inferential Analysis Results Drug Liking Visual Analog Scale (VAS) item "At this moment, my liking of this drug is" for Qualification/Baseline and Four Challenge sessions (Completer Population) for CAM2038 q1w, 32 mg, where values can range from 0 (strong disliking) to 100 (strong liking) and 50 is the neutral point. Higher scores mean worse outcome.
Time Frame	17 days

Outcome Measure Data

Analysis Population Description

Mean Drug Liking VAS Scores over Time for CAM2038 q1w 32 mg by Hydromorphone Challenge Session, Completer Population (N=24)

Arm/Group Title	CAM2038 q1w, 32 mg - Hydromorphone 6 Mg-Hydromorphone 0 mg	CAM2038 q1w, 32 mg - Hydromorphone 18 mg- Hydromorphone 0mg	CAM2038 q1w, 32 mg - Hydromorphone 18 mg- Hydromorphone 6 mg
Arm/Group Description	CAM2038 q1w 32 mg will be administered by subcutaneous injection on Day 0 and Day 7. Hydromorphone 0 mg (placebo) and 6 mg intramuscular injection will be administered on 2 of the 3 days during baseline and 4 challenge sessions on Days -3--1,1-3, 4-6, 8-10 and 11-13.	CAM2038 q1w 32 mg will be administered by subcutaneous injection on Day 0 and Day 7. Hydromorphone 18 mg and Hydromorphone 0 mg intramuscular injection will be administered on 2 of the 3 days during baseline and4 challenge sessions on Days -3--1, 1-3, 4-6, 8-10 and 11-13.	CAM2038 q1w 32 mg will be administered by subcutaneous injection on Day 0 and Day 7. Hydromorphone 18 mg and Hydromorphone 6 mg intramuscular injection will be administered on 2 of the 3 days during baseline and 4 challenge sessions on Days -3--1, 1-3, 4-6, 8-10 and 11-13.
Measure Participants	24	24	24
Qualification/Baseline	26.7 (2.40)	40.3 (2.40)	13.7 (2.40)
Days 1-3	0.9 (1.05)	2.4 (1.05)	1.5 (1.05)
Days 4-6	1.5 (1.05)	4.5 (1.05)	3.0 (1.05)
Days 8 -10	0.5 (1.05)	2.5 (1.05)	2.0 (1.05)
Days 11-13	1.0 (1.05)	3.6 (1.05)	2.6 (1.05)

5. Secondary Outcome

Title	Inferential Analysis Results for Unipolar High Visual Analog Scale (VAS) for Maximum Effect (Emax) (Completer Population)
Description	Inferential Analysis Results for Unipolar High Visual Analog Scale (VAS) for Maximum Effect (Emax) (Completer Population) comparing hydromorphone challenge doses in each of the baseline and four challenge sequence with each other, presented as Least Squares (LS) Mean with Standard Error (SE) and 95% Confidence Interval (CI). VAS item "At this moment, I feel high" where values can range from 0 (Not at all High) to 100 (Extremely High).
Time Frame	15 days

Outcome Measure Data

Analysis Population Description

Completer Population

Arm/Group Title	CAM2038 q1w, 24 mg	CAM2038 q1w, 32 mg
Arm/Group Description	CAM2038 q1w 24 mg will be administered by subcutaneous injection on Day 0 and Day 7.	CAM2038 q1w 32 mg will be administered by subcutaneous injection on Day 0 and Day 7.
Measure Participants	22	24
Baseline HMO 6mg-HMO 0mg	62.4	47.3
Baseline HMO18mg-HMO 0 mg	84.6	77.0
Baseline HMO 18mg - HMO 6mg	22.2	29.7
Challenge Session 1 HMO 6mg - HMO 0mg	4.3	3.1
Challenge Session 1 HMO 18mg - HMO 0mg	3.6	3.2
Challenge Session 1 HMO 18mg-HMO 6mg	-0.8	0.1
Challenge Session 2 HMO 6mg - HMO 0mg	1.8	1.5
Challenge Session 2 HMO 18mg - HMO 0mg	15.3	6.5
Challenge Session 2 HMO 18mg - HMO 6mg	13.5	5.0
Challenge Session 3 HMO6mg - HMO 0mg	2.6	0.9
Challenge Session 3 HMO 18mg - HMO 0mg	3.9	5.4
Challenge Session 3 HMO 18mg - HMO 6mg	1.3	4.5
Challenge Session 4 HMO 6mg - HMO 0mg	2.1	1.3
Challenge Session 4 HMO 18mg - HMO 0mg	6.4	6.0
Challenge Session 4 HMO 18mg - HMO 6mg	4.2	4.7

6. Secondary Outcome

Title	Inferential Analysis Results for Unipolar Good Drug Effects Visual Analog Scale (VAS) for Maximum Effect (Emax) (Completer Population)
Description	Inferential Analysis Results for Unipolar Good Drug Effects Visual Analog Scale (VAS) for Maximum Effect (Emax) (Completer Population) comparing hydromorphone challenge doses in each of the baseling and four challenge sequences with each other, presented as Least Squares (LS) Mean with Standard Error (SE) and 95% Confidence Interval (CI). VAS item "At this moment, I feel good drug effects" where values can range from 0 (Not at all ) to 100 (Extremely).
Time Frame	15 days

Outcome Measure Data

Analysis Population Description

Completer Population

Arm/Group Title	CAM2038 q1w, 24 mg	CAM2038 q1w, 32 mg
Arm/Group Description	CAM2038 q1w 24 mg will be administered by subcutaneous injection on Day 0 and Day 7.	CAM2038 q1w 32 mg will be administered by subcutaneous injection on Day 0 and Day 7.
Measure Participants	22	24
Baseline HMO 6mg-HMO 0mg	61.6	52.8
Baseline HMO 18mg-HMO 0mg	85.4	81.8
Baseline HMO18mg-HMO 6mg	23.9	29.1
Challenge Session 1 HMO 6mg - HMO 0mg	0.8	2.8
Challenge Session 1 HMO 18mg - HMO 0mg	1.3	4.9
Challenge Session 1 HMO 18mg-HMO 6mg	0.6	2.1
Challenge Session 2 HMO 6mg - HMO 0mg	1.8	1.7
Challenge Session 2 HMO 18mg - HMO 0mg	15.8	7.3
Challenge Session 2 HMO18mg - HMO 6mg	14.0	5.6
Challenge Session 3 HMO6mg - HMO 0mg	2.4	0.8
Challenge Session 3 HMO 18mg - HMO 0mg	4.7	4.9
Challenge Session 3 HMO 18mg - HMO 6mg	2.3	4.1
Challenge Session 3 HMO 6mg - HMO 0mg	2.2	0.7
Challenge Session 4 HMO 18mg - HMO 0mg	7.1	6.0
Challenge Session 4 HMO 18mg - HMO 6mg	4.9	5.2

7. Secondary Outcome

Title	Analysis of Treatment Phase Unipolar Bad Drug Effects Visual Analog Scale (VAS) for Maximum Effect (Emax) in 24 mg CAM2038 q1w Group (Completer Population)
Description	Analysis of Treatment Phase Unipolar Bad Drug Effects Visual Analog Scale (VAS) for Maximum Effect (Emax) in 24 mg CAM2038 q1w group (Completer Population) , presented as Least Squares (LS) mean with Standard Error (SE) for all 3 doses of hydromorphone in baseline and 4 Challenge Sessions. VAS item "At this moment, I feel bad effects" where values can range from 0 (Not at all) to 100 (Extremely).
Time Frame	15 days

Outcome Measure Data

Analysis Population Description

Completer Population

Arm/Group Title	CAM2038 q1w, 24 mg - Hydromorphone 0 mg	CAM2038 q1w, 24 mg - Hydromorphone 6 mg	CAM2038 q1w, 24 mg - Hydromorphone 18 mg
Arm/Group Description	CAM2038 q1w 24 mg will be administered by subcutaneous injection on Day 0 and Day 7. Hydromorphone 0mg (placebo) intramuscular injection will be administered on one day of the 3 days during baseline and 4 challenge sessions on Days -3--1, 1-3, 4-6, 8-10 and 11-13.	CAM2038 q1w 24 mg will be administered by subcutaneous injection on Day 0 and Day 7. Hydromorphone 6 mg intramuscular injection will be administered on one day of the 3 days during baseline and 4 challenge sessions on Days -3--1, 1-3, 4-6, 8-10 and 11-13.	CAM2038 q1w 24 mg will be administered by subcutaneous injection on Day 0 and Day 7. Hydromorphone 18 mg intramuscular injection will be administered on one day of the 3 days during baseline and 4 challenge sessions on Days -3--1, 1-3, 4-6, 8-10 and 11-13.
Measure Participants	22	22	22
Baseline	3.0 (3.18)	8.4 (3.18)	13.1 (3.18)
Challenge Session 1 (Days 1-3)	5.0 (1.17)	0.9 (1.17)	0.8 (1.17)
Challenge Session 2 (Days 4-6)	1.5 (1.17)	0.8 (1.17)	1.6 (1.17)
Challenge Session 3 (Days 8-10)	0.8 (1.17)	0.7 (1.17)	1.6 (1.17)
Challenge Session 4 (Days 11-13)	1.0 (1.17)	1.0 (1.17)	0.9 (1.17)

8. Secondary Outcome

Title	Analysis of Treatment Phase Unipolar Bad Drug Effects Visual Analog Scale (VAS) for Maximum Effect (Emax) in 32 mg CAM2038 q1w Group (Completer Population)
Description	Analysis of Treatment Phase Unipolar Bad Drug Effects Visual Analog Scale (VAS) for Maximum Effect (Emax) in 32 mg CAM2038 q1w group (Completer Population) , presented as Least Squares (LS) mean with Standard Error (SE) for all 3 doses of hydromorphone in baseline and 4 Challenge Sessions. VAS item "At this moment, I feel bad effects" where values can range from 0 (Not at all) to 100 (Extremely).
Time Frame	15 days

Outcome Measure Data

Analysis Population Description

Completer Population

Arm/Group Title	CAM2038 q1w, 32 mg - Hydromorphone 0 mg	CAM2038 q1w, 32 mg - Hydromorphone 6 mg	CAM2038 q1w, 32 mg - Hydromorphone 18 mg
Arm/Group Description	CAM2038 q1w 32 mg will be administered by subcutaneous injection on Day 0 and Day 7. Hydromorphone 0 mg (placebo) intramuscular injection will be administered on one day of the 3 days during baseline and 4 challenge sessions on Days -3--1, 1-3, 4-6, 8-10 and 11-13.	CAM2038 q1w 32 mg will be administered by subcutaneous injection on Day 0 and Day 7. Hydromorphone 6 mg intramuscular injection will be administered on one day of the 3 days during baseline and 4 challenge sessions on Days -3--1, 1-3, 4-6, 8-10 and 11-13.	CAM2038 q1w 32 mg will be administered by subcutaneous injection on Day 0 and Day 7. Hydromorphone 18 mg intramuscular injection will be administered on one day of the 3 days during baseline and 4 challenge sessions on Days -3--1, 1-3, 4-6, 8-10 and 11-13.
Measure Participants	24	24	24
Baseline	5.9 (3.47)	13.1 (3.47)	12.6 (3.47)
Challenge Session 1 (Days 1-3)	1.2 (0.67)	1.3 (0.67)	1.4 (0.67)
Challenge Session 2 (Days 4-6)	0.5 (0.67)	1.4 (0.67)	2.1 (0.67)
Challenge Session 3 (Days 8-10)	0.6 (0.67)	0.8 (0.67)	2.8 (0.67)
Challenge Session 4 (Days 11-13)	0.6 (0.67)	1.0 (0.67)	1.3 (0.67)

9. Secondary Outcome

Title	Analysis Results for Unipolar Desire to Use Visual Analog Scale (VAS) for Maximum Effect (Emax) (Completer Population)
Description	Analysis Results for Desire to Use Visual Analog Scale (VAS) for Maximum Effect (Emax) (Completer Population) comparing hydromorphone challenge doses in each of the baseline and four challenge sequence with each other, presented as Least Squares (LS) Mean with Standard Error (SE) and 95% Confidence Interval (CI). VAS item "At this moment, I desire opiods" where values can range from 0 (Definitely not) to 100 (Definitely so).
Time Frame	15 days

Outcome Measure Data

Analysis Population Description

(Completer Population)

Arm/Group Title	CAM2038 q1w, 24 mg	CAM2038 q1w, 32 mg
Arm/Group Description	CAM2038 q1w 24 mg will be administered by subcutaneous injection on Day 0 and Day 7.	CAM2038 q1w 32 mg will be administered by subcutaneous injection on Day 0 and Day 7.
Measure Participants	22	24
Baseline HMO 6mg-HMO 0mg	-18.0 (4.50)	14.1 (3.76)
Baseline HMO 18mg-HMO 0mg	-31.0 (4.50)	-29.2 (3.75)
Baseline HMO18mg-HMO 6mg	013.0 (4.50)	-15.1 (3.75)
Challenge Session 1 HMO 6mg - HMO 0mg	-0.2 (4.03)	8.7 (5.09)
Challenge Session 1 HMO 18mg - HMO 0mg	1.8 (4.03)	-5.7 (5.08)
Challenge Session 1 HMO 18mg-HMO 6mg	2.0 (4.03)	-14.4 (5.08)
Challenge Session 2 HMO 6mg - HMO 0mg	-3.8 (4.03)	-3.1 (5.09)
Challenge Session 2 HMO 18mg - HMO 0mg	-6.2 (4.03)	0.7 (5.08)
Challenge Session 2 HMO 18mg - HMO 6mg	-2.4 (4.03)	3.7 (5.08)
Challenge Session 3 HMO6mg - HMO 0mg	-2.8 (4.03)	2.2 (5.09)
Challenge Session 3 HMO 18mg - HMO 0mg	-1.8 (4.03)	0.4 (5.08)
Challenge Session 3 HMO 18mg - HMO 6mg	1.0 (4.03)	-1.8 (5.08)
Challenge Session 4 HMO 6mg - HMO 0mg	-2.2 (4.03)	-0.2 (5.09)
Challenge Session 4 HMO 18mg - HMO 0mg	-4.5 (4.03)	0.9 (5.08)
Challenge Session 4 HMO 18mg - HMO 6mg	-2.3 (4.03)	1.1 (5.08)

10. Secondary Outcome

Title	Analysis Results for Bipolar Alertness/Drowsiness Visual Analog Scale (VAS) for Maximum Effect (Emax) (Completer Population)
Description	Analysis Results for Bipolar Alertness/Drowsiness Visual Analog Scale (VAS) for Maximum Effect (Emax) (Completer Population) presented as Least Squares (LS) mean with Standard Error (SE) for all 3 doses of hydromorphone in baseline and 4 Challenge Sessions. VAS item "At this moment, my mental state is" where values can range from 0 (Very Drowsy) to 100 (Very alert), with 50 being neutral (Neither drowsy nor alert).
Time Frame	15 days

Outcome Measure Data

Analysis Population Description

(Completer Population)

Arm/Group Title	CAM2038 q1w, 24 mg	CAM2038 q1w, 32 mg
Arm/Group Description	CAM2038 q1w 24 mg will be administered by subcutaneous injection on Day 0 and Day 7.	CAM2038 q1w 32 mg will be administered by subcutaneous injection on Day 0 and Day 7.
Measure Participants	22	24
Baseline HMO 6mg-HMO 0mg	-18.0 (4.5)	-14.1 (3.76)
Baseline HMO 18mg-HMO 0mg	-31.0 (4.50)	-29.2 (3.75)
Baseline HMO18mg-HMO 6mg	-13.0 (4.50)	-15.1 (3.75)
Challenge Session 1 HMO 6mg - HMO 0mg	-2.2 (3.89)	1.7 (3.05)
Challenge Session 1 HMO 18mg - HMO 0mg	-4.9 (3.89)	-0.8 (3.05)
Challenge Session 1 HMO 18mg-HMO 6mg	-2.8 (3.89)	-2.5 (3.05)
Challenge Session 2 HMO 6mg - HMO 0mg	-6.2 (3.89)	-2.0 (3.05)
Challenge Session 2 HMO 18mg - HMO 0mg	-8.3 (3.89)	-2.7 (3.05)
Challenge Session 2 HMO 18mg - HMO 6mg	-2.1 (3.89)	-0.7 (3.05)
Challenge Session 3 HMO6mg - HMO 0mg	-0.2 (3.89)	-0.9 (3.05)
Challenge Session 3 HMO 18mg - HMO 0mg	-7.5 (3.89)	-4.3 (3.05)
Challenge Session 3 HMO 18mg - HMO 6mg	-7.4 (3.89)	-3.4 (3.05)
Challenge Session 4 HMO 6mg - HMO 0mg	0.7 (3.89)	1.8 (3.05)
Challenge Session 4 HMO 18mg - HMO 0mg	-2.1 (3.89)	-0.2 (3.05)
Challenge Session 4 HMO 18mg - HMO 6mg	-2.8 (3.89)	-2.0 (3.05)

11. Secondary Outcome

Title	Analysis Results for Unipolar Any Drug Effects Visual Analog Scale (VAS) for Maximum Effect (Emax) (Completer Population)
Description	Analysis Results for Unipolar Any Drug Effects Visual Analog Scale (VAS) for Maximum Effect (Emax) (Completer Population) presented as Least Squares (LS) mean with Standard Error (SE) for all 3 doses of hydromorphone in baseline and 4 Challenge Sessions. VAS item "At this moment, I fell any drug effects" where values can range from 0 (Not at all) to 100 (Extremely).
Time Frame	15 days

Outcome Measure Data

Analysis Population Description

(Completer Population)

Arm/Group Title	CAM2038 q1w, 24 mg	CAM2038 q1w, 32 mg
Arm/Group Description	CAM2038 q1w 24 mg will be administered by subcutaneous injection on Day 0 and Day 7.	CAM2038 q1w 32 mg will be administered by subcutaneous injection on Day 0 and Day 7.
Measure Participants	22	24
Baseline HMO 6mg-HMO 0mg	63.2 (4.49)	47.8 (5.25)
Baseline HMO 18mg-HMO 0mg	83.9 (4.49)	76.4 (5.24)
Baseline HMO18mg-HMO 6mg	20.7 (4.49)	28.6 (5.24)
Challenge Session 1 HMO 6mg - HMO 0mg	4.0 (2.27)	3.2 (2.36)
Challenge Session 1 HMO 18mg - HMO 0mg	3.5 (2.27)	6.8 (2.35)
Challenge Session 1 HMO 18mg-HMO 6mg	-0.5 (2.27)	3.6 (2.35)
Challenge Session 2 HMO 6mg - HMO 0mg	1.6 (2.27)	3.6 (2.36)
Challenge Session 2 HMO 18mg - HMO 0mg	13.6 (2.27)	5.9 (2.35)
Challenge Session 2 HMO 18mg - HMO 6mg	11.9 (2.27)	2.2 (2.35)
Challenge Session 3 HMO6mg - HMO 0mg	2.4 (2.27)	-1.1 (2.36)
Challenge Session 3 HMO 18mg - HMO 0mg	4.6 (2.27)	3.3 (2.35)
Challenge Session 3 HMO 18mg - HMO 6mg	2.2 (2.27)	4.4 (2.35)
Challenge Session 4 HMO 6mg - HMO 0mg	1.5 (2.27)	-1.1 (2.36)
Challenge Session 4 HMO 18mg - HMO 0mg	6.9 (2.27)	2.1 (2.35)
Challenge Session 4 HMO 18mg - HMO 6mg	5.4 (2.27)	3.2 (2.35)

Adverse Events

Time Frame	All AEs were documented and followed from the time the patient had signed the informed consent form until 14 days after the Follow-up Visit (or 30 days after Early Termination). The maximum number of days being 61 days.
Arm/Group Title	CAM2038 q1w, 24 mg		CAM2038 q1w, 32 mg
Arm/Group Description	CAM2038 q1w 24 mg will be administered by subcutaneous injection on Day 0 and Day 7. Hydromorphone 0 mg (placebo), 6 mg, and 18 mg intramuscular injections each being administered on one day of the 3 days during baseline and 4 challenge sessions on Days -3--1, 1-3, 4-6, 8-10 and 11-13.		CAM2038 q1w 32 mg will be administered by subcutaneous injection on Day 0 and Day 7. Hydromorphone 0 mg (placebo), 6 mg, and 18 mg intramuscular injections each being administered on one day of the 3 days during baseline and 4 challenge sessions on Days -3--1, 1-3, 4-6, 8-10 and 11-13.
All Cause Mortality
	CAM2038 q1w, 24 mg		CAM2038 q1w, 32 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/22 (0%)		0/25 (0%)
Serious Adverse Events
	CAM2038 q1w, 24 mg		CAM2038 q1w, 32 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/22 (0%)		0/25 (0%)
Other (Not Including Serious) Adverse Events
	CAM2038 q1w, 24 mg		CAM2038 q1w, 32 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/22 (59.1%)		24/25 (96%)
Cardiac disorders
Ventricular Tachycardia	0/22 (0%)		2/25 (8%)
Gastrointestinal disorders
Constipation	3/22 (13.6%)		6/25 (24%)
Nausea	1/22 (4.5%)		3/25 (12%)
Faeces Hard	0/22 (0%)		2/25 (8%)
General disorders
Injection Site Pain	2/22 (9.1%)		3/25 (12%)
Injection Site Erythema	2/22 (9.1%)		2/25 (8%)
Injection Site Pruritus	1/22 (4.5%)		2/25 (8%)
Injection site Haemorrhage	0/22 (0%)		2/25 (8%)
Nervous system disorders
Headache	3/22 (13.6%)		1/25 (4%)
Skin and subcutaneous tissue disorders
Dermatitis Contac	1/22 (4.5%)		2/25 (8%)
Acne	0/22 (0%)		2/25 (8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.