A Comparison of How Likely it is That Different Tablets of Oxycodone Will be Broken up and Snorted by Adults Who Sometimes Take Drugs for Pleasure

NCT03765346 | Completed Phase 1

• 2 other identifiers: HP7030-03U1111-1203-4920
• Study Type: interventional
• Target: 123
• Locations: 1 country
• Sites: 1

Brief Summary

The trial comprises an Enrollment Visit, a Qualification Phase, a Treatment Phase (including 3 treatment periods), a Final Examination, and a Follow-up Phone Call. The Qualification Phase includes a naloxone challenge test (to verify that participants are not opioid-dependent) and a drug discrimination test (to determine whether or not participants are able to distinguish intranasally administered active drug from placebo). Participants will be randomized to receive a single intranasal dose each of oxycodone active pharmaceutical ingredient (API) and matching placebo in a double-blind manner. The total mass of each single dose will be 30 milligrams. Participants who successfully complete the Qualification Phase are eligible to be included in the Treatment Phase. During the Treatment Phase, participants will receive test product, comparator, and placebo following a randomized, double-blind, double-dummy, 3-way crossover design. Participants will receive a single intranasal dose of each of the treatments (combined doses of investigational medicinal product {IMP}) on Day 1, Day 4, and Day 7 of the Treatment Phase. A single dose of a treatment is defined as insufflation of single doses of the 2 applicable IMPs in quick succession. The 2 applicable IMPs must be insufflated in the following pre-defined order. Oxycodone API or placebo to match oxycodone API must always be insufflated first. Oxycodone immediate release (IR) abuse-deterrent formulation (ADF) or placebo to match oxycodone IR ADF must always be insufflated second. The total mass of each single dose of treatment will be 570 milligrams.

Conditions

Substance Abuse

Keywords

intranasal abuse; abuse-deterrent

Outcome Measures

Primary Outcomes (1)

• Peak effect (Emax) for Drug Liking "at this moment".

  100-point bipolar visual analog scale (VAS) ratings after each IMP administration in response to the statement "At this moment, my liking for this drug is". The 100 millimeter (mm) bipolar VAS is anchored in the center with a neutral anchor of "neither like nor dislike" (score of 50 mm), to the left with "strong disliking" (score of 0 mm) and to the right with "strong liking" (score of 100 mm).

  at 0.16, 0.33, 0.5, 0.75, 1, 1.33, 1.66, 2, 3, 4, 6, 8, 10, 12 hours, and 24 hours post-dose on Day 1 to 2; Day 4 to 5; and Day 7 to 8

Secondary Outcomes (14)

• Maximum Plasma Concentration (Cmax) of oxycodone

  pre-dose and at 0.16, 0.33, 0.5, 0.75, 1, 1.33, 1.66, 2, 3, 4, 6, 8, 10, 12 hours, and 24 hours post-dose on Day 1 to 2; Day 4 to 5; and Day 7 to 8

• Area under the plasma concentration-time curve of oxycodone from time point 0 to t (AUC0-t)

  pre-dose and at 0.16, 0.33, 0.5, 0.75, 1, 1.33, 1.66, 2, 3, 4, 6, 8, 10, 12 hours, and 24 hours post-dose on Day 1 to 2; Day 4 to 5; and Day 7 to 8

• Area under the plasma concentration-time curve of oxycodone from time point 0 to infinity (AUC)

  pre-dose and at 0.16, 0.33, 0.5, 0.75, 1, 1.33, 1.66, 2, 3, 4, 6, 8, 10, 12 hours, and 24 hours post-dose on Day 1 to 2; Day 4 to 5; and Day 7 to 8

• High: 100-point unipolar VAS

  at 0.16, 0.33, 0.5, 0.75, 1, 1.33, 1.66, 2, 3, 4, 6, 8, 10, 12 hours, and 24 hours post-dose on Day 1 to 2; Day 4 to 5; and Day 7 to 8

• Overall Drug Liking: 100-point bipolar VAS

  at 12 and 24 hours post-dose on Day 1 to 2; Day 4 to 5; and Day 7 to 8

Study Arms (3)

Oxycodone IR ADF and placebo to match oxycodone API

EXPERIMENTAL

Participants receive a single intranasal dose of placebo to match oxycodone API powder (mass of 30 mg) followed by a single intranasal dose of manipulated oxycodone IR ADF (mass of 540 mg, containing oxycodone hydrochloride 30 mg).

Drug: Oxycodone IR ADF; Drug: Placebo to match oxycodone API powder

Oxycodone API and placebo to match oxycodone IR ADF

ACTIVE COMPARATOR

Participants receive a single intranasal dose of oxycodone API powder (mass of 30 mg, containing oxycodone hydrochloride 30 mg) followed by a single intranasal dose of placebo to match manipulated oxycodone IR ADF (mass of 540 mg).

Drug: Oxycodone API powder; Drug: Placebo to match manipulated oxycodone IR ADF.

Placebo to match oxycodone API and to match oxycodone IR ADF

PLACEBO COMPARATOR

Participants receive a single intranasal dose of placebo to match oxycodone API powder (mass of 30 mg) followed by a single intranasal dose of placebo to match manipulated oxycodone IR ADF (mass of 540 mg).

Drug: Placebo to match oxycodone API powder; Drug: Placebo to match manipulated oxycodone IR ADF.

Interventions

Oxycodone IR ADF DRUG

Oxycodone IR ADF manipulated/crushed (mass of 540 mg, containing oxycodone hydrochloride 30 mg), in a standardized procedure.

Oxycodone IR ADF and placebo to match oxycodone API

Oxycodone API powder DRUG

Oxycodone API powder (mass of 30 mg), containing oxycodone hydrochloride 30 mg.

Oxycodone API and placebo to match oxycodone IR ADF

Placebo to match oxycodone API powder DRUG

Placebo to match oxycodone API powder (mass of 30 mg).

Oxycodone IR ADF and placebo to match oxycodone API; Placebo to match oxycodone API and to match oxycodone IR ADF

Placebo to match manipulated oxycodone IR ADF. DRUG

Placebo to match oxycodone IR ADF, manipulated (mass of 540 mg).

Oxycodone API and placebo to match oxycodone IR ADF; Placebo to match oxycodone API and to match oxycodone IR ADF

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Participants have given written informed consent to participate.
• Female or male participants, aged 18 years to 55 years inclusive at the time of the Enrollment Visit.
• Body mass index between 20 kilograms per square meter and 32 kilograms per square meter inclusive, with a minimum body weight of 55 kilograms.
• Participants must be in good health as determined by the medical history, physical and laboratory examinations and must not show any clinically significant findings as determined by 12-lead electrocardiogram (ECG), vital signs (pulse rate, respiratory rate, systolic and diastolic blood pressure), oxygen saturation, body temperature, and safety laboratory parameters (hematology, clinical chemistry, clotting, and urinalysis).
• Female participants of childbearing potential must agree to use one of the acceptable contraceptive regimens listed below from at least 15 days prior to the first administration of IMP until at least 30 days after the last administration of IMP.
• For female participants of childbearing potential:
• Combined (estrogen- and progestogen-containing) hormonal contraception.
• Progestogen-only hormonal contraception associated with inhibition of ovulation.
• An intra-uterine device (hormone-free).
• An intra-uterine hormone releasing system.
• Bilateral tubal occlusion.
• Double barrier methods (i.e., male condom in addition to diaphragm, spermicide, or contraceptive sponge).
• All female participants are considered to be of childbearing potential unless they have undergone hysterectomy or bilateral oophorectomy or have been postmenopausal for at least 12 months (i.e., spontaneous amenorrhea at least 1 year prior to screening and confirmed follicle-stimulating hormone \[FSH\] level above 40 international units per liter).
• Current opioid users who have used opioids for recreational (non-therapeutic) purposes, i.e., for psychoactive effects, at least 10 times in their lifetime and at least once in the last 12 weeks before the Enrollment Visit.
• Participants who have intranasally insufflated drugs for recreational (non-therapeutic) purposes at least 3 times in the last 12 months before the Enrollment Visit.

You may not qualify if:

• Resting pulse rate below 50 beats per minute or above 100 beats per minute.
• Resting systolic blood pressure below 90 mmHg or above 140 mmHg. Resting diastolic blood pressure above 90 mmHg.
• Prolongation of the corrected QT interval (Fridericia), i.e., QTcF above 450 milliseconds, or presence of other of risk factors for torsade de pointes (e.g., heart failure, hypokalemia).
• Evidence for thyroid disease based on clinical and safety laboratory findings, including thyroid-stimulating hormone (TSH).
• Any laboratory value (from blood samples taken at the Enrollment Visit) meeting the following criteria:
• Out-of-reference range value for serum creatinine or clotting parameter prothrombin international normalized ratio.
• Out-of-reference range value for any other safety laboratory parameter that is judged by the investigator to be clinically relevant.
• Positive or missing virus serology test for human immunodeficiency virus Type 1 or Type 2 antibodies and antigen, hepatitis B surface antigen, hepatitis B core antigen antibodies, or hepatitis C virus antibodies.
• For female participants: positive or missing pregnancy test.
• Participant received an IMP or an investigational medical device in another clinical trial less than 30 days before the Enrollment Visit. Depending on the nature of the previous IMP or investigational medical device, a longer washout may be needed.
• Diseases or conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs.
• History of orthostatic hypotension.
• Known history of or at risk of seizures (i.e., head trauma, epilepsy in family history, unclear loss of consciousness).
• Definite or suspected hypersensitivity to the active substance or to any of the excipients of the IMP; especially known hypersensitivity/intolerance or contraindications to opioids (including \[history of\] bronchial asthma, chronic obstructive pulmonary disease, pulmonary heart disease, diseases of the adrenal gland, paralytic ileus, prostatic hypertrophy, or urethral stricture), opioid antagonists, or any excipients of the drug formulation.
• Any hint of chronic drug abuse, e.g., injection site (not related to trial procedures).

Sponsors & Collaborators

• Grünenthal GmbH: lead

Study Sites (1)

Algorithme Pharma

Montreal, H3P 3P1, Canada

Location

MeSH Terms

Conditions

Substance-Related Disorders

Condition Hierarchy (Ancestors)

Chemically-Induced Disorders; Mental Disorders

Study Officials

• Grünenthal Study Director

  Grünenthal GmbH

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2018
• First Posted: December 5, 2018
• Study Start: July 24, 2018
• Primary Completion: November 5, 2018
• Study Completion: November 5, 2018
• Last Updated: December 5, 2018

Record last verified: 2018-12

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)