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Trial record 17 of 17 for:    acute porphyria | "Acute intermittent porphyria"

Assessment of Intra-subject Variability in the Bioavailability of Chlorpromazine Hydrochloride

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ClinicalTrials.gov Identifier: NCT02943213
Recruitment Status : Completed
First Posted : October 24, 2016
Results First Posted : October 13, 2017
Last Update Posted : November 14, 2017
Sponsor:
Collaborator:
Parexel
Information provided by (Responsible Party):
Cycle Pharmaceuticals Ltd.

Brief Summary:

Cycle Pharmaceuticals Ltd. (Cycle) is developing an oral tablet formulation of Chlorpromazine Hydrochloride and intends to conduct bioequivalence trials to demonstrate its similarity to the RLD.

The aim of this pilot study is to investigate intrasubject variability in the bioavailability of Chlorpromazine Hydrochloride 25 mg sugar coated tablets.

Cycle aims to demonstrate that Chlorpromazine Hydrochloride has a shallow dose response curve and a wide safety margin. This will then allow for the modification of bioequivalence acceptance criteria in future pivotal studies which will reduce the number of participants required whilst still maintaining assurance of safety and efficacy.

Pilot Subjects (n): 20 Periods: 2 (2xR) Dosing: Single-dose Strength: 25 mg Test Product: N/A Reference: USL PHARMA Chlorpromazine Hydrochloride Analytes (in plasma): Chlorpromazine; 7-Hydroxychlorpromazine Bioequivalence based on 90% CI (Cmax, AUC): Standard; 80.00 - 125.00%


Condition or disease Intervention/treatment Phase
Anti-Psychotic Management of Manifestations of Psychotic Disorders Treatment of Schizophrenia Control Nausea and Vomiting Relief of Restlessness and Apprehension Before Surgery Acute Intermittent Porphyria Adjunct in the Treatment of Tetanus Control Manifestations of the Manic Type of Mani-depressive Illness Relief of Intractable Hiccups Drug: Chlorpromazine Hydrochloride Phase 1

Detailed Description:

This will be a single-dose, open-label, two-period replicate pilot study with orally administered chlorpromazine hydrochloride 25 mg (sugar coated tablets) conducted under fasting conditions in at least 16 healthy male and female subjects at a single study center.

Up to 20 eligible subjects will be enrolled in the study with 16 evaluable subjects to complete the study.

Analytes to be measured will be Chlorpromazine and 7-hydroxy-Chlorpromazine (free) as stipulated by FDA Guidance for assessment of bioequivalence for Chlorpromazine.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: A Single Center, Single Dose, Open-Label, Two-Period Replicate Pilot Study to Investigate Intra-subject Variability in the Bioavailability of a Formulation Containing Chlorpromazine Hydrochloride (25 mg Sugar Coated Tablets) in at Least 16 Healthy Males and Females Under Fasting Conditions
Study Start Date : November 2016
Actual Primary Completion Date : December 2016
Actual Study Completion Date : December 2016


Arm Intervention/treatment
Experimental: Treatment Period 1
First dosing period in which all enrolled subjects are administered a single dose of 25 mg Chlorpromazine Hydrochloride Tablet.
Drug: Chlorpromazine Hydrochloride
Chlorpromazine Hydrochloride (25 mg Tablet) - Generic US Applicant holder is USL Pharma Inc.
Other Name: Trade name: Chlorpromazine Hydrochloride 25 mg Tablets, USP

Experimental: Treatment Period 2
Second dosing period in which all enrolled subjects are administered a single dose of 25 mg Chlorpromazine Hydrochloride Tablet.
Drug: Chlorpromazine Hydrochloride
Chlorpromazine Hydrochloride (25 mg Tablet) - Generic US Applicant holder is USL Pharma Inc.
Other Name: Trade name: Chlorpromazine Hydrochloride 25 mg Tablets, USP




Primary Outcome Measures :
  1. Maximum Observed Plasma Concentration (Cmax) - Chlorpromazine [ Time Frame: 0, 0.5, 1, 1.3, 1.6, 2, 2.5, 3, 4, 5, 6, 9, 12, 16, 24, 36, 48, 72 and 96 hours ]
    Time Frame = sampling times.

  2. Maximum Observed Plasma Concentration (Cmax) - 7-Hydroxy-Chlorpromazine [ Time Frame: 0, 0.5, 1, 1.3, 1.6, 2, 2.5, 3, 4, 5, 6, 9, 12, 16, 24, 36, 48, 72 and 96 hours ]
    Time Frame = sampling times.

  3. Area Under the Plasma Concentration Versus Time Curve, From Time Zero to t, Where t is the Time of the Last Quantifiable Concentration (AUC(0-t)) - Chlorpromazine [ Time Frame: 0, 0.5, 1, 1.3, 1.6, 2, 2.5, 3, 4, 5, 6, 9, 12, 16, 24, 36, 48, 72 and 96 hours ]
    Time Frame = sampling times.

  4. Area Under the Plasma Concentration Versus Time Curve, From Time Zero to t, Where t is the Time of the Last Quantifiable Concentration (AUC(0-t)) - 7-Hydroxy-Chlorpromazine [ Time Frame: 0, 0.5, 1, 1.3, 1.6, 2, 2.5, 3, 4, 5, 6, 9, 12, 16, 24, 36, 48, 72 and 96 hours ]
    Time Frame = sampling times.

  5. Area Under the Plasma Concentration Versus Time Curve, With Extrapolation to Infinity (AUC(0-∞)) - Chlorpromazine [ Time Frame: 0, 0.5, 1, 1.3, 1.6, 2, 2.5, 3, 4, 5, 6, 9, 12, 16, 24, 36, 48, 72 and 96 hours ]
    Time Frame = sampling times.

  6. Area Under the Plasma Concentration Versus Time Curve, With Extrapolation to Infinity (AUC(0-∞)) - 7-Hydroxy-Chlorpromazine [ Time Frame: 0, 0.5, 1, 1.3, 1.6, 2, 2.5, 3, 4, 5, 6, 9, 12, 16, 24, 36, 48, 72 and 96 hours ]
    Time Frame = sampling times.


Secondary Outcome Measures :
  1. Time to Maximum Observed Plasma Concentration (Tmax) - Chlorpromazine [ Time Frame: 0, 0.5, 1, 1.3, 1.6, 2, 2.5, 3, 4, 5, 6, 9, 12, 16, 24, 36, 48, 72 and 96 hours ]
    Time Frame = sampling times

  2. Time to Maximum Observed Plasma Concentration (Tmax) - 7-Hydroxy-Chlorpromazine [ Time Frame: 0, 0.5, 1, 1.3, 1.6, 2, 2.5, 3, 4, 5, 6, 9, 12, 16, 24, 36, 48, 72 and 96 hours ]
    Time Frame = sampling times

  3. Terminal Elimination Rate Constant (λz) - Chlorpromazine [ Time Frame: 0, 0.5, 1, 1.3, 1.6, 2, 2.5, 3, 4, 5, 6, 9, 12, 16, 24, 36, 48, 72 and 96 hours ]
    Time Frame = sampling times

  4. Terminal Elimination Rate Constant (λz) - 7-Hydroxy-Chlorpromazine [ Time Frame: 0, 0.5, 1, 1.3, 1.6, 2, 2.5, 3, 4, 5, 6, 9, 12, 16, 24, 36, 48, 72 and 96 hours ]
    Time Frame = sampling times

  5. Apparent Terminal Elimination Half-life (t1/2) - Chlorpromazine [ Time Frame: 0, 0.5, 1, 1.3, 1.6, 2, 2.5, 3, 4, 5, 6, 9, 12, 16, 24, 36, 48, 72 and 96 hours ]
    Time Frame = sampling times

  6. Apparent Terminal Elimination Half-life (t1/2) - 7-Hydroxy-Chlorpromazine [ Time Frame: 0, 0.5, 1, 1.3, 1.6, 2, 2.5, 3, 4, 5, 6, 9, 12, 16, 24, 36, 48, 72 and 96 hours ]
    Time Frame = sampling times



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Healthy males and females, 18 to 65 years (both inclusive) at signing of informed consent.
  2. Body Mass Index (BMI) between 18.5 and 30 kg/m2 (both inclusive).
  3. Body mass not less than 50 kg.
  4. 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.
  5. Non-smokers.
  6. 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 postmenopausal 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.

    OR

    • 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. Examples of reliable methods of contraception include non-hormonal intrauterine device, and barrier methods combined with an additional contraceptive method.

    In this study the concomitant use of hormonal contraceptives is NOT allowed. Other methods, if considered by the investigator as reliable, will be accepted.

  7. Written consent given for participation in the study.

Exclusion Criteria:

  1. 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.
  2. Current alcohol use > 21 units of alcohol per week for males and > 14 units of alcohol per week for females.
  3. Consumption of more than 5 cups of coffee (or equivalent amounts of caffeine) per day.
  4. Regular exposure to substances of abuse (other than alcohol) within the past year.
  5. 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.

  6. Participation in another study with an experimental drug, where the last administration of the previous IMP was within 8 weeks (or within 10 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.
  7. 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.
  8. A major illness during the 3 months before commencement of the screening period.
  9. History of hypersensitivity or allergy to the IMP or its excipients or any related medication including phenothiazines or other anti-psychotics or anti-emetics.
  10. History of extrapyramidal symptoms.
  11. History of liver or renal dysfunction, epilepsy, Parkinson's disease, hypothyroidism, cardiac failure, phaeochromocytoma, myasthenia gravis, prostate hypertrophy.
  12. Familial history of deep vein thrombosis.
  13. Hereditary problems of galactose intolerance, Lapp lactase deficiency.
  14. History of QT prolongation or signs of QT prolongation on ECG.
  15. History of bronchial asthma or any other bronchospastic disease.
  16. History of convulsions.
  17. History of porphyria.
  18. Relevant history or laboratory or clinical findings indicative of acute or chronic disease, likely to influence study outcome.
  19. Donation or loss of blood equal to or exceeding 500 mL during the 8 weeks before the first administration of IMP.
  20. Diagnosis of hypotension made during the screening period.
  21. Diagnosis of hypertension made during the screening period or current diagnosis of hypertension.
  22. Resting pulse of > 100 beats per minute or < 40 beats per minute during the screening period, either supine or standing.
  23. Positive testing for HIV and Hepatitis B and Hepatitis C.
  24. Positive urine screen for drugs of abuse. In case of a positive result the urine screen for drugs of abuse may be repeated once at the discretion of the investigator.
  25. Positive urine screen for tobacco use.
  26. Female subjects that are pregnant (positive pregnancy test) or breastfeeding.
  27. Difficulty in swallowing.
  28. Any specific investigational product safety concern.
  29. Vulnerable subjects, e.g., persons in detention.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02943213


Locations
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South Africa
Farmovs Parexel
Bloemfontein, Kampuslaan Suid, South Africa, 9300
Sponsors and Collaborators
Cycle Pharmaceuticals Ltd.
Parexel
Investigators
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Principal Investigator: Dr. Yolandi Swart, FCPHM(SA) Bloemfontein Early Phase Clinical Unit, PAREXEL International (South Africa)

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Responsible Party: Cycle Pharmaceuticals Ltd.
ClinicalTrials.gov Identifier: NCT02943213     History of Changes
Other Study ID Numbers: CT-004
PXL231486 ( Other Identifier: PAREXEL (Clinical Trial Unit) )
First Posted: October 24, 2016    Key Record Dates
Results First Posted: October 13, 2017
Last Update Posted: November 14, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: participants are healthy volunteers.

Keywords provided by Cycle Pharmaceuticals Ltd.:
Chlorpromazine
Hydrochloride
Chlorpromazine Hydrochloride
Bioavailability
Variability
Variable
Absorption
USL Pharma
USL
Healthy
South Africa
Cycle
Anti-Psychotic

Additional relevant MeSH terms:
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Porphyrias
Porphyria, Acute Intermittent
Porphyrias, Hepatic
Schizophrenia
Vomiting
Mental Disorders
Psychotic Disorders
Psychomotor Agitation
Depression
Depressive Disorder
Schizophrenia Spectrum and Other Psychotic Disorders
Signs and Symptoms, Digestive
Signs and Symptoms
Metabolic Diseases
Liver Diseases
Digestive System Diseases
Skin Diseases, Genetic
Genetic Diseases, Inborn
Skin Diseases
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Psychomotor Disorders
Neurobehavioral Manifestations
Behavioral Symptoms
Mood Disorders
Chlorpromazine
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents