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Inhalers for Double-Blind Clinical Trials
Author: Martin Lamb – VP Business Development – CTS Global.
Summary:
The world market for asthma treatment was valued at $11.5 billion in 2003, a figure which is expected to almost double to $20.9 billion by 2010. Within the same timeframe the global market for chronic obstructive pulmonary disease (COPD) is expected to more than treble from $2.3 billion to $7.4 billion. Treatment for these respiratory conditions can be inhaled (such as inhaled beta agonists, corticosteroids and combinations) or taken orally (such as Leukotriene antagonists). The former is most widely used and, with the exception of Merck’s Singulair (oral), accounts for almost all of the market-leading therapies for asthma and COPD. need to ‘blind’ their own product and perform all of the associated analytical ensure that the results of these trials are formulation minus the active ingredient. statistically valid, it would be preferable to perform these trials in a double-blind differences are so extreme? Modification Producing a straight placebo copy of the feasible because the inhaler plays such a and trademarks, is not possible for legal from the trial drug. However, since it is Clinical Study Design
product in its planned market form. This the active ingredient and propellants, and it is generally labelled according to the
Double-Blind =
instruction (such as ‘shake before use’ in the local language). Additional markings Double-Dummy =
capsule OR Placebo A tablet and Active B Capsule their own inhaler, it is not possible to do this for the comparator. However, in the active comparator. The key difference is This is usually a large plastic actuator be used on very few occasions because it is rare to find two MDIs close enough in active ingredients and insert materials. important that the comparator units used in a clinical trial are distinct from the placebo, so should appear different from to the production of clinical trial supplies aerosol-filling capabilities, it is possible Blinding Metered Dose Inhalers (MDIs)
produced in-house. In most instances, it is possible to match exactly the size and These inhalers consist of a plastic body aerosol by identifying the parts used in canister is inserted. The aerosol contains Various methods are available to achieve manufacturer. If this is the case, parts taken into account. If such a scenario is unlikely, a slight difference may not be placebo units so that they are different If sourcing placebo aerosols from a third used, though we rarely see this approach delays to clinical trials. First, allow time copy these. The only way to obtain these significant, so minimising the number of these substantially reduces the unit cost Dry-Powder Inhalers (DPIs)
drug in the airways. Examples of leading DPIs include GSK’s diskhaler/accuhaler blinding strategies are required for each. difference, it is necessary to cover the Capsule-based DPIs
Active powders for Boehringer’s Spiriva and Novartis’s Foradil are provided in hard gelatine capsules. In order to take a dose of these products, patients remove a weights for these products are generally capsule from a blister pack insert it into very low, and the accuracy and nature of Converting the inhaler unit itself for use in a trial is fairly straight forward, and problems. Blister packs are branded, and technology not available to most clinical produce the blisters (such as tropicalised readily sourced, these lack the printing result, it is necessary to remove printing only at time of use’), and the fact that blisters in high-barrier films, suggest that Reservoir-based DPIs
affect its stability. Analytical support for the process is therefore essential, and it turbohaler design, contain a reservoir of powder containing the active ingredient. convert these units to placebo simply by However, there are complications in this involves selecting an inert filler that has behaviour to the active blend contained in commercial capsules. Particle size Blister-Based DPIs
employing blister strips to deliver active accuhaler/diskhaler. This unit employs a 60-dose blister strip, with a specific dose of drug in each blister pocket. Each time a patient takes a dose they pull a trigger, next full pocket and the dose counter to complex, and therefore the most difficult invested millions of dollars in a robotic assembling these units. Replicating this technology in a typical clinical supplies thousand, placebo units for clinical trials approaches can be developed, these still placebo powder, but this approach is not Conclusions
patient, so replacing powder simply adds inhalers to placebos. As a result, it is essential that planning for this type of proposed clinical trial start date. Even if or obscured on each unit so that clinical time is available, the cost of automating such a process for a one-off comparative study is huge. If a trial requires only a few thousand comparator inhaler units to be converted to placebo, this can result in very high costs for each unit
produced. It is worth bearing in mind
that while this cost may be a barrier to
an in-house clinical supplies department
working on a limited number of trials, it
may be less of a barrier to a contractor
working with several companies with
several trials each. By spreading the cost
of developing and equipping this process
across several clients and trials, a
contractor may be more willing to invest
in developing one of these conversion
processes. From the industry’s
perspective, outsourcing production of
placebo units could bring double-blind
inhaler studies within reach.

For more information about Clinical
Trials Services contact:
E-mail: [email protected]
or log onto:
Web: www.cts-almac.com

Source: http://www.almacgroup.com/wp-content/uploads/Inhalers_for_double-blind_CTs2.pdf