Diazepam Buccal Film (DBF) - Diastat Rectal Gel (DRG) Crossover Study

NCT03953820 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 180323
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 3

Brief Summary

This was a multiple centers, single-dose, open-label, randomized two-sequence crossover, two-period study to evaluate the pharmacokinetics (PK) of single doses of Diazepam Buccal Film (DBF) compared with Diastat® Rectal Gel (DRG) under fed conditions in adult male and female participants on a stable concomitant regimen of anti-epileptic drugs for the treatment of epilepsy.

Conditions

Epilepsy

Outcome Measures

Primary Outcomes (3)

• AUC 0-t

  Area Under Plasma Concentration-Time Curve From Time Zero to the last non-zero concentration

  0.5, 0.75, 1, 105, 2, 3, 4, 6, 9, 12, 24, 48, 72, 96, 120, 144, 192, and 240 hours post-dose

• AUC 0-inf

  Area under concentration time curve, from time 0 extrapolated to infinity

  0.5, 0.75, 1, 105, 2, 3, 4, 6, 9, 12, 24, 48, 72, 96, 120, 144, 192, and 240 hours post-dose

• Cmax

  Maximum observed plasma concentration

  0.5, 0.75, 1, 105, 2, 3, 4, 6, 9, 12, 24, 48, 72, 96, 120, 144, 192, and 240 hours post-dose

Study Arms (3)

Diazepam Buccal Film, Then Diastat Rectal Gel

EXPERIMENTAL

Participants received a single dose of Diazepam Buccal Film following a moderate-fat meal and then received a single dose of Diastat Rectal Gel following a moderate-fat meal with a 28-day washout between doses.

Drug: Diazepam Buccal Film; Drug: Diastat® Rectal Gel (Valeant Pharmaceuticals USA)

Diastat Rectal Gel, Then Diazepam Buccal Film

EXPERIMENTAL

Participants received a single dose of Diastat Rectal Gel following a moderate-fat meal and then received a single dose of Diazepam Buccal Film following a moderate-fat meal with a 28-day washout between doses.

Drug: Diazepam Buccal Film; Drug: Diastat® Rectal Gel (Valeant Pharmaceuticals USA)

Diazepam Buccal Film following a High-Fat Meal

EXPERIMENTAL

Participants who volunteered to participate in the second period received a second dose of Diazepam Buccal Film at the same dose and exactly the same manner as the earlier dose with the exception that the dose was administered following ingestion of a high-fat meal.

Drug: Diazepam Buccal Film

Interventions

Diazepam Buccal Film DRUG

Diazepam Buccal Film administered on inner aspect of the cheek at the recommended dose regimen (10 mg to 17.5 mg according to body weight) following ingestion of a moderate fat meal and following ingestion of a high-fat meal.

Also known as: DBF

Diastat Rectal Gel, Then Diazepam Buccal Film; Diazepam Buccal Film following a High-Fat Meal; Diazepam Buccal Film, Then Diastat Rectal Gel

Diastat® Rectal Gel (Valeant Pharmaceuticals USA) DRUG

Diastat Rectal Gel administered rectally according to product label administration and dosing instructions (10 mg to 20 mg according to body weight) following ingestion of a moderate-fat meal.

Also known as: DRG

Diastat Rectal Gel, Then Diazepam Buccal Film; Diazepam Buccal Film, Then Diastat Rectal Gel

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, smoker (no more than 25 cigarettes or equivalent daily) or non-smoker, ≥ 18 and ≤ 65 years of age, with body weight between 38 and 111 kg, inclusive. Potential subjects with weights in the range of 112 to 134 kg (247 - 249 pounds) may be allowed to participate in the study at the discretion of the Principal Investigator.
• On a stable and ongoing regimen of at least one AED for treatment of epilepsy. Stable regimen is defined as no change in AED regimen for at least 30 days before the first study drug administration and no change anticipated in the prescribed AED regimen over the course of study participation.
• Subjects must have a diagnosis of seizure disorder (any seizure type or frequency) under treatment with at least one AED.
• Healthy (except for seizure disorder), according to the medical history, ECG, vital signs, laboratory results and physical examination as determined by the Principal Investigator/Sub- Investigator.
• Clinical laboratory values within local laboratories acceptable ranges, unless values are deemed by the Principal Investigator/Sub-Investigator as "Not Clinically Significant".
• Ability to comprehend and be informed of the nature of the study, as assessed by clinic staff.
• Availability to volunteer for the entire study duration and willing to adhere to all protocol requirements.
• Agree not to have a tattoo or tongue or body piercing until the end of the study.
• Agree not to drive or operate heavy machinery if feeling dizzy or drowsy following drug administration until full mental alertness is regained.
• Subjects must be able and willing to remove denture or bracing at the time of dosing.
• Non-vasectomized male subjects must use two forms of medically accepted method of contraception with all sexual partners of childbearing potential during the study and for 111 days following the last dose of study drug. Medically accepted effective forms of contraception include:
• simultaneous use of a male condom and
• for the female partner, hormonal contraceptives (used since at least 4 weeks) or intrauterine contraceptive device (placed since at least 4 weeks) or diaphragm or cervical cap with intravaginally applied spermicide.
• Male subjects must be willing not to donate sperm until 111 days following the last study drug administration.
• Female subjects who are sexually active with a non-sterile male partner (sterile male partners are defined as men vasectomized since at least 6 months) must fulfill at least one of the following:

You may not qualify if:

• Clinically significant abnormal laboratory test results found during medical screening.
• Positive pregnancy test at screening.
• Known presence of any clinically significant: hepatic (e.g. hepatic impairment), renal/genitourinary (renal impairment, kidney stones), gastrointestinal (e.g. ulcerative colitis, ileus, partial or complete intestinal blockage, appendicitis), cardiovascular (e.g. uncontrolled hypertension), cerebrovascular, pulmonary, endocrine (controlled diabetes is acceptable), immunological, musculoskeletal, neurological (other than known seizure disorder), psychiatric, dermatological or hematological disease or condition unless determined as not clinically significant by the Principal Investigator/Sub-Investigator and confirmed by Sponsor via written communication prior to subject enrollment.
• Presence of any clinically significant gastrointestinal pathology (e.g. chronic diarrhea, inflammatory bowel disease), unresolved gastrointestinal symptoms (e.g. diarrhea, vomiting), or other conditions known to interfere with the absorption, distribution, metabolism or excretion of the study drug experienced within 7 days prior to first study drug administration, as determined by the Principal Investigator/Sub-Investigator.
• Any clinically significant rectal abnormality by history or physical examination, or any condition, for which, in the judgment of the Principal Investigator/Sub-Investigator, administration of rectal gel would cause a potential risk to the subject.
• Baseline levels of concomitant AED outside of the acceptable therapeutic range at screening.
• Presence of any clinically significant illness within 30 days prior to first study drug administration, as determined by the Principal Investigator/Sub-Investigator.
• Presence of any clinically significant physical or organ abnormality as determined by the Principal Investigator/Sub-Investigator.
• Presence of any clinically significant lesion of the oral cavity.
• Clinically significant ECG abnormalities (QTcF interval \> 450 msec for males or QTcF interval \> 470 msec for females) or vital sign abnormalities (systolic blood pressure lower than 90 or over 160 mmHg, diastolic blood pressure lower than 50 or over 100 mmHg, or heart rate less than 50 or over 100 bpm) at screening, unless deemed otherwise by the Principal Investigator/Sub-Investigator.
• A positive test result for HIV, Hepatitis B surface antigen, Hepatitis C.
• A positive test result for any of the following: drugs of abuse (amphetamines, methamphetamines, barbiturates, cocaine, opiates, phencyclidine, tetrahydrocannabinol,MDMA, methadone, and benzodiazepines, except where a positive test is consistent with a stable regimen of a prescribed medication) and alcohol breath test.
• Known history or presence of:
• Alcohol abuse or dependence within one year prior to screening;
• Drug abuse or dependence;

Sponsors & Collaborators

• Aquestive Therapeutics: lead

Study Sites (3)

Clinical Trials of Florida, LLC

Miami, Florida, 33186, United States

Location

Bioclinica Research

Orlando, Florida, 32806, United States

Location

Florida Premier Research Institute, LLC

Winter Park, Florida, 32789, United States

Location

MeSH Terms

Conditions

Epilepsy

Interventions

Diagnosis-Related Groups

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Prospective Payment System; Reimbursement Mechanisms; Insurance, Health, Reimbursement; Financing, Organized; Economics; Health Care Economics and Organizations

Results Point of Contact

• Title: Denis Scheper, Director of Portfolio Management and Clinical Operations
• Organization: Aquestive Therapeutics

denis.scheper@aquestive.com

(908)941-1887

Study Officials

• Gary Slatko, MD

  Aquestive Therapeutics

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study consisted of 2 periods. In Period 1 , participants received a single dose of Diazepam Buccal Film or Diastat Rectal Gel in a randomized sequence following a moderate fat meal with a 28-day washout between doses. Subjects who completed Period 1 were asked to participate in a second period (Period 2) on a voluntary basis. Those subjects who agreed to participate in Period 2 received a second dose of DBF in exactly the same dose and manner as the earlier dose with the exception it was administered following a high fat meal.

Study Record Dates

• First Submitted: April 26, 2019
• First Posted: May 17, 2019
• Study Start: April 13, 2019
• Primary Completion: July 31, 2019
• Study Completion: July 31, 2019
• Last Updated: August 18, 2020
• Results First Posted: August 18, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)