Bioequivalence Study of Sulfadoxine/ Pyrimethamine Dispersible Tablets in Healthy Subjects Under Fasting Conditions

Phase 1

• Conditions: Bioequivalence
• Interventions: Drug: G-COSPE® tablets; Drug: Sulfadoxine/Pyrimethamine dispersible tablets, 250 mg sulfadoxine / 12.5 mg pyrimethamine & 500 mg sulfadoxine / 25 mg pyrimethamine

• Registration Number: NCT05497063
• Lead Sponsor: Emzor Pharmaceutical Industries Limited

Brief Summary

To asses bio equivalence between two (500 mg sulfadoxine / 25 mg pyrimethamine) formulation

Detailed Description

• The aim of this study is to assess bioequivalence between a single dose from the test product, Sulfadoxine/Pyrimethamine two dispersible tablets (250 mg sulfadoxine / 12.5 mg pyrimethamine), manufactured by Emzor Pharmaceuticals Industries Ltd, Nigeria versus the reference product G-COSPE® one tablet (500 mg sulfadoxine / 25 mg pyrimethamine) manufactured by Guilin Pharmaceutical Co. Ltd, China.

Study Timeline

• Study First Submitted: 2022-05-01
• Status Verified: 2022-08
• Study First Submitted QC: 2022-08-09
• Last Update Submitted: 2022-08-09
• Study First Posted: 2022-08-11
• Last Update Posted: 2022-08-11
• Study Start: 2022-12
• Primary Completion: 2023-02
• Study Completion: 2023-02

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 70

Inclusion Criteria

• 1. The subject is Caucasian & aged between eighteen & fifty years (18 - 50), both inclusive.

  2. The subject is within the limits for his/her height & weight as defined by the body mass index range (18.5 - 30.0 Kg/m2).

  3. The subject is willing to undergo the necessary pre- & post- medical examinations set by this study.

  4. Results of medical history, vital signs, physical examination & conducted medical laboratory tests are normal as per appendix 3.

  5. The subject tested negative for hepatitis (B & C) viruses and human immunodeficiency virus (HIV).

  6. There is no history or evidence of psychiatric disorder, antagonistic personality, and 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.

  7. The subject is able to understand and willing to sign the informed consent form.

  8. The subject has normal liver (AST & ALT enzymes) function. 9. The subject's kidney function tests are within normal ranges. As per appendix 3.

  9. The subject has normal respiratory system. 11. The subject's folic acid levels are within normal range. 12. The subject has normal platelet levels. As per appendix 3. 13. For female subjects: negative pregnancy test and the woman is using two reliable contraception methods during the study and until 52 days after dosing.

Note: Pyrimethamine/sulfadoxine showed reproductive toxicity in animal studies. Pyrimethamine/sulfadoxine should not be used during the first trimester of pregnancy unless the benefit is considered to outweigh the risks and alternative drugs are not available. During 2nd or 3rd trimesters of pregnancy, may be used for intermittent preventive treatment in pregnancy.

14. The subject has normal cardiovascular system, ECG recording & QTc interval less than 450 ms.

Exclusion Criteria

• 1. The subject is a heavy smoker (more than 10 cigarettes per day). 2. The subject has suffered an acute illness one week before dosing. 3. The subject has a history of or concurrent consumption of alcohol. 4. The subject has a history of or concurrent consumption of illicit drugs. 5. The subject has a history of hypersensitivity and/or contraindications to the study drug and any related compounds.

  2. Subject who has been hospitalized within three months before the study or during the study.

  3. Subject who is vegetarian. 8. The subject has consumed caffeine or xanthine containing beverages or foodstuffs within two days before dosing and until 72 hours after dosing.

  4. The subject has taken a prescription medication within two weeks or even an over the counter product (OTC) within one week before dosing and any time during the study, unless otherwise judged acceptable by the clinical investigator.

  5. The subject has taken grapefruit containing beverages or foodstuffs within seven (7) days before dosing and any time during the study.

  6. The subjects who have been participating in any clinical study (e.g. pharmacokinetics, bioavailability and bioequivalence studies) within the last 80 days prior to the present study 12. The subjects who have donated blood within 80 days before first dosing. 13. The subject has a history of G6PD Deficiency. 14. The subject has a history presence of cardiovascular, pulmonary, renal, hepatic, gastrointestinal, hematological, endocrinal, immunological, dermatological, neurological, musculoskeletal or psychiatric diseases.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
G-COSPE® tablets, 500 mg sulfadoxine / 25 mg pyrimethamine	G-COSPE® tablets	One tablet of G-COSPE® tablets, 500 mg sulfadoxine / 25 mg pyrimethamine to be given as single dose once under fasting condition
Sulfadoxine/Pyrimethamine dispersible tablets, 250 mg sulfadoxine / 12.5 mg pyrimethamine	Sulfadoxine/Pyrimethamine dispersible tablets, 250 mg sulfadoxine / 12.5 mg pyrimethamine & 500 mg sulfadoxine / 25 mg pyrimethamine	Two dispersible tablets of Sulfadoxine/Pyrimethamine (250 mg sulfadoxine / 12.5 mg pyrimethamine to be given as single dose once under fasting condition

Primary Outcome Measures

Name	Time	Method
Bioequivalence based on Peak Plasma Concentration (Cmax) for Sulfadoxine and Pyrimethamine.	72 hours	The average bioequivalence of the products will be concluded if the two-sided 90 % confidence interval for the test to reference ratio of the population means is within 80.00 - 125.00 % for the ln transformed data Cmax of sulfadoxine \& pyrimethamine
Area under the plasma concentration versus time curves (AUC0 - 72) for Sulfadoxine and Pyrimethamine	72 hours	The average bioequivalence of the products will be concluded if the two-sided 90 % confidence interval for the test to reference ratio of the population means is within 80.00 - 125.00 % for the ln transformed data AUC0 -72 of sulfadoxine \& pyrimethamine

Secondary Outcome Measures

Name	Time	Method
Obtaining the Tmax (Time to reach maximum concentration) for Sulfadoxine and Pyrimethamine	72 hours	The descriptive statistics including Maximum, Minimum and Median values will be measured for Tmax
Number of participant with treatment related adverse events as assessed by CTCAE v4.0.	At the end of the study (at 72.00 hours post dosing	Hematology (Safety and Tolerability) Hematology test will include Complete blood count