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

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT02943213
• Date of registration: 21/10/2016
• Prospective Registration: Yes
• Primary sponsor: Cycle Pharmaceuticals Ltd.
• Public title: Assessment of Intra-subject Variability in the Bioavailability of Chlorpromazine Hydrochloride
• Scientific 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
• Date of first enrolment: November 2016
• Target sample size: 20
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02943213
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Single Group Assignment. Primary purpose: Basic Science. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

South Africa

Contacts

• Name: Dr. Yolandi Swart, FCPHM(SA)
• Affiliation: Bloemfontein Early Phase Clinical Unit, PAREXEL International (South Africa)

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

Anti-Psychotic

Management of Manifestations of Psychotic Disorders

Relief of Intractable Hiccups

Control Nausea and Vomiting

Acute Intermittent Porphyria

Adjunct in the Treatment of Tetanus

Control Manifestations of the Manic Type of Mani-depressive Illness

Relief of Restlessness and Apprehension Before Surgery

Treatment of Schizophrenia

Intervention(s)

Drug: Chlorpromazine Hydrochloride

Primary Outcome(s)

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]

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]

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]

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]

Area Under the Plasma Concentration Versus Time Curve, With Extrapolation to Infinity (AUC(0-8)) - 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]

Area Under the Plasma Concentration Versus Time Curve, With Extrapolation to Infinity (AUC(0-8)) - 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]

Secondary Outcome(s)

Terminal Elimination Rate Constant (?z) - 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 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 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]

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]

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]

Terminal Elimination Rate Constant (?z) - 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]

Secondary ID(s)

CT-004

PXL231486

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Parexel

Results

• Results available: Yes
• Date Posted: 13/10/2017
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02943213