Bioequivalence Study of Two Oral Haloperidol Tablets Formulations in Healthy Subjects Under Fed Conditions

NCT04411953 | Completed Phase 1 Results

• 2 other identifiers: CT-0060145FRM18
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose on this study was to determine whether the test product, Haloperidol Tablets, 2 mg (Cycle Pharmaceuticals Ltd), and the reference product, Haloperidol Tablets, United States Pharmacopeia (USP), 2 mg (Mylan Pharmaceuticals Inc.) are bioequivalent under fed conditions.

Conditions

Bioequivalence

Outcome Measures

Primary Outcomes (3)

• Concentration Maximum (Cmax)

  The maximum observed concentration of haloperidol as measured by bioanalysis of the blood plasma is referred to as the Cmax.

  pre-dose (0 hours), and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16, 24, 30, 36, 48, 72, 96, 120, 144, 168, 192 hours post dose

• Area Under the Curve (0-t) (AUC(0-t))

  Area under the plasma concentration versus time curve from time zero to t, where t is the time of the timepoint of the last quantifiable concentration of haloperidol in the blood plasma. The curve is constructed by plotting the concentration of haloperidol in the blood plasma against the time for each blood sample.

  pre-dose (0 hours), and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16, 24, 30, 36, 48, 72, 96, 120, 144, 168, 192 hours post dose

• Area Under the Curve(0-∞) (AUC(0-∞))

  Area under the plasma concentration versus time curve from time zero to ∞, where ∞ is the timepoint of the last quantifiable concentration of haloperidol in the blood plasma, plus it's elimination rate constant. AUC(0-∞) = AUC(0-t) + AUC(t-∞).

  pre-dose (0 hours), and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16, 24, 30, 36, 48, 72, 96, 120, 144, 168, 192 hours post dose

Secondary Outcomes (3)

• Time to Maximum Concentration (Tmax)

  pre-dose (0 hours), and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16, 24, 30, 36, 48, 72, 96, 120, 144, 168, 192 hours post dose

• Terminal Elimination Rate Constant (λz)

  pre-dose (0 hours), and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16, 24, 30, 36, 48, 72, 96, 120, 144, 168, 192 hours post dose

• Terminal Elimination Half-life (t½)

  pre-dose (0 hours), and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16, 24, 30, 36, 48, 72, 96, 120, 144, 168, 192 hours post dose

Study Arms (2)

Reference Product (Treatment A)

ACTIVE COMPARATOR

Subjects received Haloperidol Tablets 2 mg Reference Product (Mylan Pharmaceuticals Inc.). Subjects also received as pre-medication Benztropine Mesylate Tablets, USP (1 mg every 10 to 12 hours), beginning 4 to 6 hours before dosing with IMP and continued for a total of 4 doses. A high-fat, high-calorie breakfast was served 30 minute before administration of the IMP.

Drug: Haloperidol Tablets, Mylan Pharmaceuticals Inc.

Test Product (Treatment B)

EXPERIMENTAL

Subjects received Haloperidol Tablets 2 mg Test Product (Cycle Pharmaceuticals Ltd). Subjects also received as pre-medication Benztropine Mesylate Tablets, USP (1 mg every 10 to 12 hours), beginning 4 to 6 hours before dosing with IMP and continued for a total of 4 doses. A high-fat, high-calorie breakfast was served 30 minute before administration of the IMP.

Drug: Haloperidol Tablets, Cycle Pharmaceuticals Ltd

Interventions

Haloperidol Tablets, Mylan Pharmaceuticals Inc. DRUG

single dose, 2 mg Haloperidol tablet

Also known as: Benztropine Mesylate Tablets

Reference Product (Treatment A)

Haloperidol Tablets, Cycle Pharmaceuticals Ltd DRUG

single dose, 2 mg Haloperidol tablet

Also known as: Benztropine Mesylate Tablets

Test Product (Treatment B)

Eligibility Criteria

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

You may qualify if:

• Body mass index (BMI) between 18.5 and 30 kg/m\^2 (both inclusive).
• Body mass not less than 50 kg.
• Medical history, vital signs, physical examination, standard 12-lead electrocardiogram (ECG) and laboratory investigations must be clinically acceptable or within laboratory reference ranges for the relevant laboratory tests, unless the investigator considers the deviation to be irrelevant for the purpose of the study.
• Non-smokers.
• Females, if:
• Not of childbearing potential, e.g., has been surgically sterilized, undergone a hysterectomy, amenorrhea for ≥ 12 months and considered post-menopausal, Note: In post-menopausal women, the value of the serum pregnancy test may be slightly increased. This test will be repeated to confirm the results. If there is no increase indicative of pregnancy, the female will be included in the study.
• Of childbearing potential, the following conditions are to be met:
• Negative pregnancy test If this test is positive, the subject will be excluded from the study. In the rare circumstance that a pregnancy is discovered after the subject received IMP, every attempt must be made to follow her to term.
• Not lactating
• Abstaining from sexual activity (if this is the usual lifestyle of the subject) or must agree to use an accepted method of contraception, and agree to continue with the same method throughout the study An example of a reliable method of contraception is a non-hormonal intrauterine device. In this study the concomitant use of hormonal contraceptives is NOT allowed. Other methods, if considered by the investigator as reliable, will be accepted.
• Written consent given for participation in the study.
• Written consent given for participation in the genetic component of the study (if performed based on Food and Drug Administration (FDA) feedback). If the subject declines participation in the genetic component, the subject will not be allowed to participate in the study.

You may not qualify if:

• Evidence of psychiatric disorder, antagonistic personality, poor motivation, emotional or intellectual problems likely to limit the validity of consent to participate in the study or limit the ability to comply with protocol requirements.
• Current alcohol use \> 21 units of alcohol per week for males and \> 14 units of alcohol per week for females (1 unit is equal to approximately 330 mL of beer, one small glass \[200 mL\] of wine, or one measure \[25 mL\] of spirits).
• Regular exposure to substances of abuse (other than alcohol) within the past year.
• Use of any medication, prescribed or over-the-counter or herbal remedies, within 2 weeks before the first administration of IMP except if this will not affect the outcome of the study in the opinion of the investigator. In this study the concomitant use of hormonal contraceptives is NOT allowed.
• Participation in another study with an experimental drug, where the last administration of the previous IMP was within 8 weeks (or within 5 elimination half-lives for chemical entities or 2 elimination half-lives for antibodies or insulin, whichever is the longer) before administration of IMP in this study, at the discretion of the investigator.
• Treatment within the previous 3 months before the first administration of IMP with any drug with a well-defined potential for adversely affecting a major organ or system.
• A major illness during the 3 months before commencement of the screening period.
• History of hypersensitivity or allergy to the IMP or its excipients or any related medication.
• History of hypersensitivity or allergy to the pre-medication or its excipients or any related medication.
• History of hypersensitivity or allergy to the rescue medication or its excipients or any related medication.
• History of bronchial asthma or any other bronchospastic disease.
• History of convulsions.
• History of porphyria.
• History of cardiac arrhythmias.
• History of sudden cardiac death in the family or history of familial long QT syndrome.

Sponsors & Collaborators

• Cycle Pharmaceuticals Ltd.: lead
• Farmovs: collaborator

Study Sites (1)

FARMOVS Clinical Research Organisation

Bloemfontein, Free State, 9301, South Africa

Location

MeSH Terms

Interventions

Benztropine

Intervention Hierarchy (Ancestors)

Tropanes; Azabicyclo Compounds; Aza Compounds; Organic Chemicals; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring

Results Point of Contact

• Title: Head of Global Regulatory Affairs and Clinical Development
• Organization: Cycle Pharmaceuticals

claudia.percivalle@cyclepharma.com

+441223803635

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: May 28, 2020
• First Posted: June 2, 2020
• Study Start: November 15, 2019
• Primary Completion: December 19, 2019
• Study Completion: December 19, 2019
• Last Updated: June 8, 2022
• Results First Posted: June 8, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

ZA (1)