Drug-drug Interaction Study of CHF5993 With Cimetidine

NCT02287272 | Completed Phase 1

• 2 other identifiers: CCD-05993AA1-122013-005491-18
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the pharmacokinetic interaction when CHF5993 (pressurized metered-dose inhaler (pMDI) is administered with Cimetidine (probe inhibitor of the organic cation transport in the kidneys), by comparing the systemic exposure (AUC0-t) of Glycopyrronium Bromide (GB), after a single dose of the fixed combination CHF 5993 pMDI administered alone or at steady-state of Cimetidine

Conditions

COPD

Keywords

COPD- cimetidine- drug-drug interaction

Outcome Measures

Primary Outcomes (1)

• Area under the plasma concentration-time curve from time 0 to the last quantifiable concentration (AUC0-t) of Glycopyrronium Bromide

  pre-dose, 5, 10,15,30min, 1,2,4,6,8,12hr post-dose

Secondary Outcomes (3)

• Other pharmacokinetic parameters for Glycopyrronium Bromide

  pre-dose-72hr post-dose

• Other pharmacokinetic parameters for Formoterol

  pre-dose-24hr post dose

• Other pharmacokinetic parameters for B17MP

  pre-dose- 72hr post-dose

Study Arms (2)

Treatment period R

ACTIVE COMPARATOR

single inhaled dose of CHF 5993 pMDI (BDP/FF/GB fixed dose combination)

Drug: CHF 5993 pMDI

Treatment period T

ACTIVE COMPARATOR

Cimetidine plus CHF5993 pMDI: repeated doses of oral cimetidine for 6 days plus a single inhaled dose of CHF 5993 pMDI (BDP/FF/GB fixed dose combination)

Drug: Cimetidine plus CHF5993 pMDI

Interventions

CHF 5993 pMDI DRUG

4 inhalations of CHF 5993 pMDI (BDP/FF/GB 100/6/25 micrograms per actuation) giving a total dose of 400, 24, 100 micrograms of BDP, FF, GB

Treatment period R

Cimetidine plus CHF5993 pMDI DRUG

Cimetidine 800 milligrams twice daily for 6 days. On the fourth day, in addition, 4 inhalations of CHF5993 pMDI (BDP/FF/GB total dose 400/24/100 micrograms)

Treatment period T

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subject's written informed consent obtained prior to any study-related procedure;
• Male and female healthy volunteers aged 18-45 years inclusive;
• Able to understand the study procedures, the risks involved and ability to be trained to correctly use the devices;
• Body Mass Index (BMI) between 18.0 and 30.0 kg/m2 inclusive;
• A serum creatinine within the normal range (0,7-1,2 mg/dL) and an eGFR \>80 mL/min/1.73 m2;
• Non- or ex-smokers who smoked \< 5 pack years (pack-years = the number of cigarette packs per day times the number of years) and stopped smoking \> 1 year;
• Good physical and mental status, determined on the basis of the medical history and a general clinical examination;

You may not qualify if:

• Female subjects: pregnant or lactating women and all women physiologically capable of becoming pregnant (i.e. women of childbearing potential) UNLESS they meet the following definition of post-menopausal: 12 months of natural (spontaneous) documented amenorrhea or are willing to use one or more of the following reliable \*methods of contraception:
• surgical sterilization (e.g. bilateral tubal ligation, hysterectomy for females; vasectomy for males)
• hormonal contraception (implantable, patch, oral), intrauterine device (IUD) or intrauterine system (IUS)
• barrier methods (male or female condom, diaphragm, sponge, cervical cap).
• Blood donation (equal or more than 450 ml) or blood loss less than 8 weeks before inhalation of the study medication;
• Positive HIV1 or HIV2 serology;
• Positive results from the Hepatitis serology which indicates acute or chronic Hepatitis B or Hepatitis C;
• History of substance abuse or drug abuse within 12 months prior to screening visit or with a positive urine drug screen at screening;
• An abnormal triplicate 12-lead ECG (QRS\> 120 msec, PR\> 220 msec, HR \< 40 bpm, HR \> 110 bpm) at screening or at randomization;
• Subjects whose electrocardiogram (12-lead ECG) shows QTcF \>450 ms for males and \>470 for females at screening or at randomization;
• Subjects whose DBP is higher than 90 mmHg or SBP is higher than 140 mmHg at screening or at randomization;
• Subjects who received any investigational new drug, or participated in clinical study within the last 8 weeks before screening;
• History of hypersensitivity to M3 Antagonists, β2-agonist, corticosteroids or any of the excipients contained in any of the formulations used in the trial;
• Treatment within the previous 3 months before the screening visit until the end of the study procedures in the last treatment period with any drug known to have a well-defined potential for hepatotoxicity (e.g. isoniazide, nimesulide, ketoconazole);
• Subjects who refuse to abstain from alcohol or xanthine containing foods or beverages or grapefruit containing foods or beverages from 48 hour prior to each intake of study medication until the end of confinement at the clinical centre;

Sponsors & Collaborators

• Chiesi Farmaceutici S.p.A.: lead

Study Sites (1)

Life Science Services SGS Belgium NV

Antwerp, 2060, Belgium

Location

Related Publications (1)

• Mariotti F, Ciurlia G, Spaccapelo L, Muraro A, Acerbi D. A Two-Period Open-Label, Single-Dose Crossover Study in Healthy Volunteers to Evaluate the Drug-Drug Interaction Between Cimetidine and Inhaled Extrafine CHF 5993. Eur J Drug Metab Pharmacokinet. 2017 Apr;42(2):269-279. doi: 10.1007/s13318-016-0345-2.

  PMID: 27209586 RESULT

Related Links

• CSR Synopsis available in the Chiesi Clinical Study Register

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Cimetidine

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Guanidines; Amidines; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Wouter Haazen, MD

  Life Science Services SGS Belgium NV

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: May 20, 2014
• First Posted: November 10, 2014
• Study Start: May 1, 2014
• Primary Completion: July 1, 2014
• Study Completion: September 1, 2014
• Last Updated: October 29, 2021

Record last verified: 2021-10

Locations

BE (1)