ATORvastatin in Pulmonary TUBerculosis: a POPulation PharmacoKinetics -PharmacoDynamics Sub-study (ATORTUB popPK-PD)

NCT07303699 | Recruiting Phase 2 DMC

• 2 other identifiers: ERC/2023/11/15/BIRB/IEC/0004553
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to assess pharmacokinetic parameters of atorvastatin at different doses when combined with the standard first line tuberculosis (TB) treatment regimen in adults with drug sensitive pulmonary TB. The pharmacokinetics parameters will be correlated with Pharmcodynamic measures and a PK/PD model that will identify an optimal dosing regimen of atorvastatin that is appropriate for the treatment of pulmonary tuberculosis will be developed.

Conditions

Pulmonary Tuberculosis (TB)

Keywords

Pulmonary TB; Pulmonary Tuberculosis; Tuberculosis; Koch's disease; Mycobacterium tuberculosis; Isoniazid; Atorvastatin; Rifampicin; Rifampin; Ethambutol; pyrazinamide; Intensive Phase; Continuation Phase; statins; Antitubercular therapy (ATT)

Outcome Measures

Primary Outcomes (3)

• Area under the plasma concentration versus time curve (AUC 0-24) for atorvastatin acid, rifampicin, isoniazid and their metabolites at steady state

  Sparse pharmacokinetic sampling will be employed during participants treatment follow up visits for the determination of plasma concentrations of atorvastatin acid, rifampicin, isoniazid. and their active metabolites (2-hydroxyl atorvastatin 4- hydroxyl atorvastatin, acetyl - isoniazid, desacetyl - rifampicin). AUC will be estimated using Population Pharmacokinetics analysis

  Sampling will be on day 14 & week 8, 16 and 24 post randomization

• Peak Plasma Concentration (Cmax) for atorvastatin acid, rifampicin, isoniazid and their metabolites at steady state

  Sparse pharmacokinetic sampling will be employed during participants treatment follow up visits for the determination of plasma concentrations of atorvastatin acid, rifampicin, isoniazid. and their active metabolites (2-hydroxyl atorvastatin 4- hydroxyl atorvastatin, acetyl - isoniazid, desacetyl - rifampicin). Cmax will be estimated using Population Pharmacokinetics analysis

  Sampling will be on day 14 & week 8, 16 and 24 post randomization

• Plasma Clearance (Cl/F) in mL/min of atorvastatin acid, rifampicin, isoniazid and their metabolites at steady state

  Sparse pharmacokinetic sampling will be employed during participants treatment follow up visits for the determination of plasma concentrations of atorvastatin acid, rifampicin, isoniazid. and their active metabolites (2-hydroxyl atorvastatin 4- hydroxyl atorvastatin, acetyl - isoniazid, desacetyl - rifampicin). Plasma clearance of aforementioned drugs and metabolites will be estimated using Population Pharmacokinetics analysis

  Sampling will be on day 14 & week 8, 16 and 24 post randomization

Secondary Outcomes (9)

• Correlation between AUC 0-24 of atorvastatin acid, 2-hydroxyl atorvastatin and 4- hydroxyl atorvastatin at steady state and days 0-14 early bactericidal activity in participants on atorvastatin-based regimens

  day 14 post randomization

• Correlation between Cmax of atorvastatin acid, 2-hydroxyl atorvastatin and 4- hydroxyl atorvastatin at steady state and days 0-14 early bactericidal activity in participants on atorvastatin-based regimens

  day 14 post randomization

• Correlation between Cmax of atorvastatin acid, 2-hydroxyl atorvastatin and 4- hydroxyl atorvastatin at steady state and time to stable sputum culture conversion

  2 - 24 weeks post randomization

• Correlation between AUC 0-24 of atorvastatin, atorvastatin acid, 2-hydroxyl atorvastatin and 4- hydroxyl atorvastatin) at steady state and change in baseline chest Xray severity score at 4, 6 and 12 months

  16 -52weeks post randomisation

• Correlation between AUC 0-24 of atorvastatin acid, 2-hydroxyl atorvastatin and 4- hydroxyl atorvastatin at steady state and time to stable sputum culture conversion

  2 - 24 weeks post randomization

Study Arms (4)

20mg atorvastatin with standard of care (SOC) for TB

EXPERIMENTAL

Trial of 20mg atorvastatin with standard of care (SOC) for TB \[2RHZE/4RH + 4AT(20)\]

Drug: Atorvastatin 20 mg; Drug: Fixed dose combination of Rifampicin (R) Isoniazid (H) Pyrazinamid (Z) Ethambutol (E)

40mg atorvastatin with standard of care (SOC) for TB

EXPERIMENTAL

Trial of 40mg atorvastatin with standard of care (SOC) for TB \[2RHZE/4RH + 4AT(40)\]

Drug: Atorvastatin 40 mg; Drug: Fixed dose combination of Rifampicin (R) Isoniazid (H) Pyrazinamid (Z) Ethambutol (E)

60mg atorvastatin with standard of care (SOC) for TB

EXPERIMENTAL

Trial of 60mg atorvastatin with standard of care (SOC) for TB \[2RHZE/4RH + 4AT(60)\]

Drug: Atorvastatin 60 mg; Drug: Fixed dose combination of Rifampicin (R) Isoniazid (H) Pyrazinamid (Z) Ethambutol (E)

standard of care (SOC) for TB

ACTIVE COMPARATOR

Standard of Care (SOC) for TB \[2RHZE/4RH\]

Drug: Fixed dose combination of Rifampicin (R) Isoniazid (H) Pyrazinamid (Z) Ethambutol (E)

Interventions

Atorvastatin 20 mg DRUG

Participants will receive 16weeks of daily oral treatment with 20mg atorvastatin 4AT(20)\]

Also known as: Astin

20mg atorvastatin with standard of care (SOC) for TB

Atorvastatin 40 mg DRUG

Participants will receive 16 weeks of daily oral treatment with 40mg atorvastatin 4AT(40)\]

Also known as: Astin

40mg atorvastatin with standard of care (SOC) for TB

Atorvastatin 60 mg DRUG

Participants will receive 16weeks of daily oral treatment with 60mg atorvastatin 4AT(60)

Also known as: Astin

60mg atorvastatin with standard of care (SOC) for TB

Fixed dose combination of Rifampicin (R) Isoniazid (H) Pyrazinamid (Z) Ethambutol (E) DRUG

Participants will receive 8 weeks of daily oral treatment with rifampin, isoniazid, pyrazinamide, ethambutol, followed by 16 weeks of daily treatment with rifampin, isoniazid \[2RHZE/4RH\]

Also known as: Stop TB Kit

20mg atorvastatin with standard of care (SOC) for TB; 40mg atorvastatin with standard of care (SOC) for TB; 60mg atorvastatin with standard of care (SOC) for TB; standard of care (SOC) for TB

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Sputum specimen positive for tubercle bacilli on Gene Xpert or direct smear microscopy
• Either no previous anti-TB chemotherapy, or less than 2 weeks of previous chemotherapy
• Aged 12years and above
• A firm home address that is readily accessible for visiting
• Agreement to participate in the study and to give a sample of blood for HIV testing
• Normal baseline laboratory values at or within 14 days prior to screening:
• Serum or plasma alanine aminotransferase (ALT) less than or equal to 3 times the upper limit of normal
• Serum or plasma total bilirubin less than or equal to 2.5 times the upper limit of normal
• Serum or plasma creatinine level less than or equal to 2 times the upper limit of normal
• Serum or plasma potassium level greater than or equal to 3.5 meq/L
• Hemoglobin level of 7.0 g/dL or greater
• Platelet count of 100,000/mm3 or greater
• Informed consent to participate in the study and to give a sample of blood for HIV testing

You may not qualify if:

• Participants known or suspected of having any form of drug resistance TB.
• Patients co infected with HIV
• Those with poor general condition where no delay in treatment can be tolerated
• Evidence of clinically significant metabolic or co morbid medical conditions ; malignancy; or other diseases like history of or current cardiovascular disorder such as heart failure, coronary heart disease, arrhythmia.
• Known or family history of bleeding disorders.
• Any renal impairment characterized by serum creatinine clearance of 1.5 x upper limit of normal of the clinical laboratory reference range at screening.
• Myositis and or Creatinine phosphokinase three times upper limit of normal
• Patient in a moribund state
• Has TB meningitis
• Presence of any of the pre-existing non-TB diseases outlined in the protocol
• Diabetes mellitus
• Hypertension
• Currently on anti TB medication
• Any other chronic illness/ co morbidities that warrants being on daily routine medications
• Presence of a psychiatric illness

Sponsors & Collaborators

• Obafemi Awolowo University Teaching Hospital: lead
• Open Philanthropy: collaborator
• Obafemi Awolowo University: collaborator

Study Sites (3)

National Tuberculosis and Leprosy Training Centre, Saye

Zaria, Kaduna State, Nigeria

RECRUITING

Federal Teaching Hospital

Katsina, Katsina State, Nigeria

RECRUITING

Obafemi Awolowo University Teaching Hospitals Complex, Ile Ife, Osun state, Nigeria

Ile-Ife, Osun State, 2345, Nigeria

RECRUITING

MeSH Terms

Conditions

Tuberculosis, Pulmonary; Tuberculosis

Interventions

Atorvastatin; Isoniazid; Protons; Pyrazinamide; Ethambutol

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids; Hydrazines; Organic Chemicals; Isonicotinic Acids; Acids, Heterocyclic; Pyridines; Cations, Monovalent; Cations; Ions; Electrolytes; Inorganic Chemicals; Hydrogen; Elements; Gases; Nucleons; Elementary Particles; Physical Phenomena; Pyrazines; Ethylenediamines; Diamines; Polyamines; Amines

Study Officials

• Olanisun O Adewole, MD

  Obafemi Awolowo University / Teaching Hospital, Ile Ife, Nigeria

  PRINCIPAL INVESTIGATOR

• Bolanle A Omotoso, MD

  Obafemi Awolowo University /Teaching Hospital, Ile- Ife, Osun State, Nigeria

  STUDY DIRECTOR

• Olanisun O Adewole, MD

  Obafemi Awolowo University /Teaching Hospital, Ile- Ife, Osun State, Nigeria

  STUDY CHAIR

Central Study Contacts

Olanisun O Adewole, MD

CONTACT

+2348034074930; adewolef@yahoo.co.uk , ola.adewole@oauife.edu.ng

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 21, 2025
• First Posted: December 26, 2025
• Study Start: January 3, 2026
• Primary Completion (Estimated): March 30, 2027
• Study Completion (Estimated): March 30, 2028
• Last Updated: January 23, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

NG (3)