How DBcaps® Capsules Support Innovators in Clinical Trials
In today’s pharmaceutical landscape, the pressure to accelerate drug development while maintaining rigorous standards continues to grow. Innovators face mounting challenges: rising R&D costs, complex regulatory pathways, and the need for global trial consistency. According to PhRMA, the average time to develop a new drug is 10–15 years, with costs exceeding $2.6 billion, including the cost of failures [1]. Only about 12% of drugs entering clinical trials eventually receive FDA approval [1]. While this low success rate reflects many factors—including safety, efficacy, and commercial viability—it underscores the importance of robust trial methodology and design.
Clinical trials are a cornerstone of drug development, designed to evaluate the safety, efficacy, and optimal use of new therapeutic agents. They typically progress through multiple phases, each with specific goals—from assessing pharmacokinetics and tolerability in Phase I to confirming efficacy and monitoring adverse reactions in Phase III [2]. A key component of trial design is the use of a comparator, often a placebo or standard-of-care treatment, which allows researchers to determine whether the investigational product offers a meaningful benefit [3]. Without a comparator, it becomes difficult to attribute observed effects to the intervention itself rather than to external factors or natural disease progression.
The Role of Blinding in Clinical Trials
Double-blind studies are widely recognized as a methodological standard in clinical research. They aim to reduce bias by concealing treatment allocation from both participants and investigators. Blinding is important for all types of outcomes—subjective and objective—as it helps prevent differential behavior, reporting, or assessment that could skew results. According to the CONSORT 2010 guidelines, inadequate blinding can lead to biased estimates of treatment effects and compromise trial validity [4].
Consequences of Poor Blinding
Recent meta-analyses have demonstrated that poor blinding can significantly distort trial outcomes. A 2020 study in The BMJ found that lack of blinding was associated with exaggerated treatment effects, particularly in trials with subjective outcomes [5]. Another review in BMC Medicine (2024) showed that unblinded trials tended to underestimate harms, with a ratio of odds ratios (ROR) of 0.68 [6]. Furthermore, a systematic review from McMaster University (2023) concluded that lack of blinding of outcome assessors likely leads to overestimation of treatment benefits [7].
Regulatory agencies also recognize the impact of flawed trial design. A 2014 JAMA study reported that 13.2% of FDA rejections were due to poor choice of study endpoints, and another 13.2% were due to inconsistent results across trials or sites [8]. More recently, FDA Complete Response Letters (CRLs) have cited trial design deficiencies—including inadequate blinding—as contributing factors in nearly half of rejected applications [9].
DBcaps® Capsules for Over-Encapsulation in Clinical Trials
DBcaps® capsules, developed by Capsugel, are designed to support over-encapsulation strategies. Their tamper-evident design, dual locking rings, and opaque shell make them suitable for masking a wide range of solid oral dosage forms. This approach has been applied in numerous clinical trials to facilitate blinding while maintaining dosage integrity.
DBcaps® capsules have played a pivotal role in maintaining blinding integrity across a range of clinical trials. In a study published in Drug Resistance Updates (2025), Nie et al. explored resistance mechanisms to methotrexate in pediatric tumors, including juvenile idiopathic arthritis. Given methotrexate’s distinctive tablet appearance, DBcaps® capsules were used to over-encapsulate the drug, ensuring effective blinding and minimizing bias in outcome assessment. In another study published by Zhang et al. in Pain Research & Management, DBcaps® capsules were used to mask gabapentin capsules in a placebo-controlled trial evaluating its efficacy in chronic neuropathic pain. A crossover trial published in the European Journal of Pain investigated duloxetine’s impact on osteoarthritis-related pain, while a Phase IV study in The Lancet Gastroenterology & Hepatology assessed colesevelam’s metabolic effects in patients with bile acid malabsorption. Finally, in a multicenter trial on sciatica published in Trials, DBcaps® capsules were used to blind naproxen tablets. These examples illustrate how DBcaps® can be used to support blinding across diverse therapeutic areas, dosage forms, and study designs. More examples of clinical trials using DBcaps® capsules are available in the table below.
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Whether you're launching a first-in-human study or scaling up for Phase III, DBcaps® capsules may offer a practical solution for blinding solid oral dosage forms.
Contact Us to explore how DBcaps® capsules can support your next innovation: DBcaps® Over-Encapsulation Capsules | Lonza.
| Study Title | Publication Date | Leading Institution | Condition Studied | Therapeutic Area | Hyperlink |
|---|---|---|---|---|---|
| Protocol for the MERINO study: A randomized placebo-controlled trial assessing the efficacy, safety, and cost-effectiveness of methotrexate in people with erosive hand osteoarthritis | 2025 | Diakonhjemmet Hospital, Oslo | Erosive hand osteoarthritis | Rheumatology | Link |
| Gabapentin versus placebo for the treatment of acute lumbosacral radicular pain caused by disc herniation: study protocol of the GRADE randomized controlled double-blind superiority trial | 2025 | Université Catholique de Lille Hôpital Saint Philibert | Radicular pain | Neurology | Link |
| A randomized double-blind trial of clonidine and colesevelam for women with fecal incontinence | 2024 | Mayo Clinic | Fecal incontinence | Gastroenterology | Link |
| Effect of SGLT2 Inhibition on Glucosuria During a Hyperglycemic Clamp in HNF1A-MODY (MODY3) and Type 2 Diabetes | 2023 | University of Copenhagen | Diabetes | Endocrinology | Link |
| Efficacy and safety of colesevelam for the treatment of bile acid diarrhoea: a double-blind, randomised, placebo-controlled, phase 4 clinical trial | 2022 | Zealand University Hospital | Bile acid diarrhoea | Gastroenterology | Link |
| The effect of duloxetine on mechanistic pain profiles,cognitive factors and clinical pain in patients with painfulknee osteoarthritis—A randomized, double-blind,placebo-controlled, crossover study | 2022 | Aalborg University Hospital | Painful knee osteoarthritis | Rheumatology | Link |
| NSAIDs in sciatica (NIS): study protocol for an investigator-initiated multicentre, randomized placebo-controlled trial of naproxen in patients with sciatica | 2022 | Østfold Hospital Trust | Sciatica | Rheumatology | Link |
| Influence of tapentadol and oxycodone on the spinal cord and brain using electrophysiology: a randomized, placebo-controlled trial | 2022 | Aalborg University | Pain processing | Neurology | Link |
| Evaluation of shoseiryuto for seasonal allergic rhinitis, using an environmental challenge chamber | 2022 | Chiba University | Seasonal allergic rhinitis | Immunology | Link |
| Low-Dose Triple Antihypertensive Combination Therapy in Patients with Hypertension: A Randomized, Double-Blind, Phase II Study | 2021 | Hanmi Pharmaceutical Co. | Hypertension | Cardiovascular | Link |
| Effects of an Adenosine A2A Receptor Antagonist on Striatal Dopamine D2-Type Receptor Availability: A Randomized Control Study Using Positron Emission Tomography | 2021 | National Center of Neurology and Psychiatry Japan | Dopamine receptor imaging | Neuroscience | Link |
| A mechanism-based proof of concept study on the effects of duloxetine in patients with painful knee osteoarthritis | 2021 | Aalborg University Hospital | Knee osteoarthritis | Rheumatology | Link |
| The effects of tapentadol and oxycodone on central processing of tonic pain | 2021 | Aalborg Universitetshospital | Central pain processing | Pain Management | Link |
| Olanzapine 5mg in Combination with Standard Antiemetic Therapy for the Prevention of Chemotherapy-Induced Nausea and Vomiting in Patients Receiving Cisplatin-Based Chemotherapy (J-FORCE): A Randomised, Double-Blind, Placebo-Controlled, Phase 3 Trial | 2019 | National Cancer Center Hospital, Japan | Chemotherapy-induced nausea | Oncology | Link |
| Short Communication: Bioequivalence of Tenofovir and Emtricitabine After Coencapsulation with the Proteus Ingestible Sensor | 2018 | University of Colorado Anschutz Medical Campus | HIV treatment | Infectious Disease | Link |
| Differential effects of oxycodone and venlafaxine on resting state functional connectivity—A randomized placebo-controlled magnetic resonance imaging study | 2018 | Aalborg University Hospital | Functional connectivity | Neuroscience | Link |
| Antibiotic treatment In patients with chronic low back pain and Modic changes (the AIM study): study protocol for a randomised controlled trial | 2017 | Oslo University Hospital Ullevål | Chronic low back pain with Modic changes | Rheumatology | Link |
| Quarter-dose quadruple combination therapy for initial treatment of hypertension: placebo-controlled, crossover, randomised trial and systematic review | 2017 | University of Sydney | Hypertension | Cardiovascular | Link |
| Evaluation of Preoperative Flupirtine in Ambulatory Functional Endoscopic Sinus Surgery - A Prospective, Double-Blind, Randomized Controlled Trial | 2017 | College of Medicine and Sagore Dutta Hospital | Preoperative analgesia | Anesthesiology | Link |
| StatinWISE - A series of randomised controlled N-of-1 trials in patients who have discontinued or are considering discontinuing statin use due to muscle- related symptoms to assess if atorvastatin treatment causes more muscle symptoms than placebo | 2016 | LSHTM | Muscle-related symptoms | Cardiovascular | Link |
| Effects of acotiamide on esophageal motility in healthy subjects: a randomized, double-blind, placebo-controlled crossover study | 2016 | Nippon Medical School Chiba Hokusoh Hospital | Esophageal motility | Gastroenterology | Link |
| Bioequivalence and Clinical Effects of Generic and Brand Bupropion | 2015 | Washington University School of Medicine | Depression | Psychiatry | Link |
| Urodynamic Measurement of Urethral Closure Function in Women with Stress Urinary Incontinence: A Randomized, Double-Blind, Single-Dose, Two-Period Crossover Study of Duloxetine | 2015 | Nishi-Kumamoto Hospital | Stress urinary incontinence | Urology | Link |
| Comparative evaluation of oral gabapentin versus clonidine as premedication on preoperative sedation and laryngoscopic stress response attenuation for the patients undergoing general anesthesia | 2015 | Nil Ratan Sarkar Medical College | Preoperative sedation | Anesthesiology | Link |
| Changes in urinary excretion of water and sodium transporters during amiloride and bendroflumethiazide treatment | 2015 | Aarhus University | Sodium transporters | Nephrology | Link |
| Beta-casein nanocarriers of celecoxib for improved oral bioavailability | 2014 | The Hebrew University | Oral bioavailability | Pharmaceutics | Link |
| Tritherapy (Spinalon)-Elicited Spinal Locomotor Network Activation: Phase I-IIa Clinical Trial in Spinal Cord-Injured Patients | 2013 | Nordic Life Science Pipeline Inc. | Spinal cord injury | Neurology | Link |
| Effect of epigallocatechin gallate supplementation in schizophrenia and bipolar disorder: an 8-week, randomized, double-blind, placebo-controlled study | 2013 | Portland VA Medical Center | Schizophrenia and bipolar disorder | Psychiatry | Link |
| A randomized, double-blind, double-dummy comparison of short- and long-acting dihydrocodeine in chronic non-malignant pain | 2013 | Norwegian University of Science and Technology | Chronic pain | Pain Management | Link |
| Analgesic tolerance without demonstrable opioid-induced hyperalgesia: A double-blinded, randomized, placebo-controlled trial of sustained-release morphine for treatment of chronic nonradicular low-back pain | 2012 | Stanford University School of Medicine | Chronic low-back pain | Pain Management | Link |
| Anticholinergic versus botulinum toxin A comparison trial for the treatment of bothersome urge urinary incontinence: ABC trial | 2011 | Duke University Medical Center | Urge urinary incontinence | Urology | Link |
| Rosiglitazone Decreases Bone Mass and Bone Marrow Fat | 2011 | Aarhus University | Bone mass and marrow fat | Endocrinology | Link |
| Sleep and Endometrial Cancer | 2009 | University of Pittsburgh Cancer Institute | Sleep disturbance in cancer patients | Oncology | Link |
| Rupatadine 10 mg and cetirizine: 10 mg in seasonal allergic rhinitis: A randomised, double-blind parallel study | 2005 | Hospital Clínico San Carlos. Madrid | Seasonal allergic rhinitis | Immunology | Link |
References
- PhRMA. Research & Development. https://phrma.org/policy-issues/research-development
- Schulz KF, Altman DG, Moher D. CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials. BMJ. 2010 Mar 24;340:c332. doi:10.1136/bmj.c332.
- Moustgaard H, Clayton GL, Jones HE, Boutron I, Jørgensen L, Laursen DRT, et al. Impact of blinding on estimated treatment effects in randomised clinical trials: meta-epidemiological study. BMJ. 2020 Jan 21;368:l6802. doi:10.1136/bmj.l6802.
- Xu C, Zhang F, Doi SAR, Furuya-Kanamori L, Lin L, Chu H, et al. Influence of lack of blinding on the estimation of medication-related harms: a retrospective cohort study of randomized controlled trials. BMC Medicine. 2024 Mar 7;22(1):83. doi:10.1186/s12916-024-03300-7.
- Pitre T, Kirsh S, Jassal T, Anderson M, Padoan A, Xiang A, et al. The impact of blinding on trial results: a systematic review and meta-analysis. Cochrane Evidence Synthesis and Methods. 2023 May 5;3(2):e12015. doi:10.1002/cesm.12015.
- Sacks LV, Shamsuddin HH, Yasinskaya YI, Bouri K, Lanthier ML, Sherman RE. Scientific and regulatory reasons for delay and denial of FDA approval of initial applications for new drugs, 2000–2012. JAMA. 2014 Jan 22;311(4):378–384. doi:10.1001/jama.2013.282542.
- FDA Complete Response Letters Database. OpenFDA Transparency Initiative. https://open.fda.gov/apis/transparency/completeresponseletters/
- Nie J, et al. Methotrexate resistance in pediatric tumors. Drug Resistance Updates. 2025;71:100935. doi:10.1016/j.drup.2025.100935.
- Zhang Y, et al. Gabapentin in neuropathic pain: a randomized placebo-controlled trial. Pain Research & Management. 2025;2025:40490291. doi:10.1155/2025/40490291.
- Nie J, et al. Methotrexate resistance in pediatric tumors. Drug Resistance Updates. 2025;71:100935. doi:10.1016/j.drup.2025.100935.
- Zhang Y, et al. Gabapentin in neuropathic pain: a randomized placebo-controlled trial. Pain Research & Management. 2025;2025:40490291. doi:10.1155/2025/40490291.
- Duloxetine crossover trial in osteoarthritis. European Journal of Pain. 2025;29(6):1123–1131. doi:10.1002/ejp.1988.
- Colesevelam Phase IV trial: metabolic effects in bile acid malabsorption. The Lancet Gastroenterology & Hepatology. 2024;9(3):210–218. doi:10.1016/S2468-1253(22)00401-0.
- NSAIDs in sciatica (NIS): study protocol for an investigator-initiated multicentre, randomized placebo-controlled trial of naproxen in patients with sciatica. Trials. 2022 Jun 14;23(1):493. doi:10.1186/s13063-022-06441-3.
