Clinical Trials

Since Provocholine is a diagnostic agent, there is great value to including methacholine challenge testing as part of clinical trial protocols.  It can have a variety of applications depending on the question that is being asked.

Methapharm has experience providing technical support for clinical trials using Provocholine in the following areas:

  • Study inclusion/exclusion criteria
  • Bioequivalence
  • Quantifying a response to investigational medications
  • Comparing inhaler devices
  • Epidemiological studies
  • Specific atopies (allergies)
  • Consumer product evaluation

The FDA have issued two guidance’s where methacholine challenge testing is discussed specifically when used in clinical trials:

Research

Research on asthma and other respiratory conditions has evolved over the years. Provocholine is frequently used as the primary outcome or in conjunction with other drugs/procedures. In recent years, research using Provocholine has been effectively used to rule out asthma in patients, especially children, given that family history and other variables are taken into consideration.

PROVOCHOLINE® (METHACHOLINE CHLORIDE USP) IS A BRONCHOCONSTRICTOR AGENT FOR DIAGNOSTIC PURPOSES ONLY AND SHOULD NOT BE USED AS A THERAPEUTIC AGENT. PROVOCHOLINE SHOULD BE ADMINISTERED ONLY BY INHALATION. SEVERE BRONCHOCONSTRICTION AND REDUCTION IN RESPIRATORY FUNCTION CAN RESULT FROM THE ADMINISTRATION OF PROVOCHOLINE. PATIENTS WITH SEVERE HYPERREACTIVITY OF THE AIRWAYS CAN EXPERIENCE BRONCHOCONSTRICTION AT A DOSAGE AS LOW AS 0.025 MG/ML (0.125 CUMULATIVE UNITS). IF SEVERE BRONCHOCONSTRICTION OCCURS, IT SHOULD BE REVERSED IMMEDIATELY BY THE ADMINISTRATION OF A RAPID ACTING INHALED BRONCHODILATOR AGENT (BETA- AGONIST). BECAUSE OF THE POTENTIAL FOR SEVERE BRONCHOCONSTRICTION, PROVOCHOLINE INHALATION CHALLENGE SHOULD NOT BE PERFORMED IN ANY PATIENT WITH CLINICALLY APPARENT ASTHMA, WHEEZING, OR VERY LOW BASELINE PULMONARY FUNCTION TESTS (e.g., FEV1 LESS THAN 1 TO 1.5 LITER OR LESS THAN 70% OF THE PREDICTED VALUES). PLEASE CONSULT STANDARD NOMOGRAMS FOR PREDICTED VALUES.1 IF A PHYSICIAN IS PERFORMING THE TEST, ANOTHER PERSON MUST BE AVAILABLE IN THE BUILDING TO GIVE ASSISTANCE IF REQUIRED; OTHERWISE A PHYSICIAN MUST BE IN THE VICINITY TO BE ABLE TO RESPOND QUICKLY. THE PATIENT MUST NEVER BE LEFT UNATTENDED DURING THE TEST. PROVOCHOLINE INHALATION CHALLENGE SHOULD BE PERFORMED ONLY UNDER THE SUPERVISION OF A PHYSICIAN TRAINED IN AND THOROUGHLY FAMILIAR WITH ALL ASPECTS OF THE TECHNIQUE OF METHACHOLINE CHALLENGE, ALL CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS, AND THE MANAGEMENT OF RESPIRATORY DISTRESS.

EMERGENCY EQUIPMENT AND MEDICATION SHOULD BE IMMEDIATELY AVAILABLE TO TREAT ACUTE RESPIRATORY DISTRESS.

REFERENCE: 1. Morris JF, Koski WA, Johnson LC. Spirometric standards for healthy non-smoking adults. Am Rev Resp Dis. Jan 1971; 103: 57-67.