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Results for “phase 3”

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PubMed2026

Phase 3 Trial of Oral Infigratinib in Children with Achondroplasia.

BACKGROUND: Achondroplasia is a genetic skeletal condition caused by FGFR3 pathogenic variants. Infigratinib, an oral FGFR1-3 tyrosine kinase inhibitor, down-regulates key pathways in the pathogenesis of achondroplasia. METHODS: In this phase 3, multicenter, double-blind, placebo-controlled trial, we randomly assigned children with achondroplasia (3 to 17 years of age) in a 2:1 ratio to receive infigratinib (at a dose of 0.25 mg per kilogram of body weight) or placebo once daily for 52 weeks. The primary end point was the change from baseline in the annualized height velocity in the infigratinib group as compared with the placebo group at week 52. Key secondary end points were the change from baseline in the height z score and in the upper-to-lower body segment ratio at week 52. The primary analysis evaluated the treatment effect at week 52 in the full analysis population, with missing data handled with a prespecified imputation approach. RESULTS: In all, 114 patients underwent randomization: 75 patients to receive infigratinib (with 1 withdrawal before treatment) and 39 patients to receive placebo. The difference between infigratinib and placebo in the least-squares mean change from baseline to week 52 was 1.74 cm per year (95% confidence interval [CI], 1.31 to 2.17; P<0.001) for the annualized height velocity, 0.32 (96% CI, 0.23 to 0.41; P<0.001) for the height z score, and -0.02 (96% CI, -0.06 to 0.01) for the upper-to-lower body segment ratio. Adverse events occurred in 71 of 74 patients (96%) in the infigratinib group and in 37 of 39 patients (95%) in the placebo group; serious adverse events occurred in 4 of 74 patients (5%) and 1 of 39 patients (3%), respectively. No serious adverse events or adverse events leading to treatment discontinuation were considered by the investigator to be related to infigratinib or placebo. CONCLUSIONS: In children with achondroplasia, treatment with once-daily oral infigratinib for 52 weeks resulted in a significantly greater increase from baseline in the annualized height velocity than placebo. (Funded by BridgeBio Pharma; PROPEL 3 ClinicalTrials.gov number, NCT06164951; EudraCT number, 2023-506130-67.).

Adolescent↗

PubMed2005

In vitro activity of tigecycline against isolates from patients enrolled in phase 3 clinical trials of treatment for complicated skin and skin-structure infections and complicated intra-abdominal infections.

The in vitro activity of tigecycline was evaluated against 4913 baseline pathogens isolated from 1986 patients enrolled in 4 pivotal phase 3 clinical trials. The trials, which were conducted in 38 countries worldwide, involved patients with complicated skin and skin-structure infections or complicated intra-abdominal infections. Tigecycline was active against the most prevalent pathogens for each infection type, including gram-positive and gram-negative strains of both aerobic and anaerobic bacteria (MICs, < or =2 microg/mL for most pathogens). The spectrum of activity of tigecycline included important pathogens, such as Staphylococcus aureus (including methicillin-resistant S. aureus), Streptococcus pyogenes, Escherichia coli, Klebsiella pneumoniae, and Bacteroides fragilis. A few genera, such as Pseudomonas aeruginosa and members of the tribe Proteeae, were generally less susceptible to tigecycline than were other gram-negative pathogens. The susceptibility of the pathogens to tigecycline was similar for isolates obtained from patients enrolled in the studies of complicated skin and skin-structure infection or of complicated intra-abdominal infection. For most pathogens, the susceptibility to tigecycline was similar across all geographic regions. The excellent expanded broad-spectrum activity of tigecycline demonstrated in vitro against clinical isolates confirmed its potential utility for pathogens associated with complicated skin and skin-structure infections or complicated intra-abdominal infections.

Anti-Bacterial Agents↗

PubMed2026

Daily low-dose carboplatin or weekly carboplatin plus nab-paclitaxel for concurrent chemoradiotherapy in older patients with locally advanced non-small cell lung cancer (JCOG1914): A randomized phase 3 trial.

BACKGROUND: Daily low-dose carboplatin with concurrent thoracic radiotherapy is the standard treatment for older patients with unresectable locally advanced non-small cell lung cancer (LA-NSCLC) in Japan. METHODS: This open-label phase 3 trial was conducted at 38 institutions in Japan. Patients aged ≥ 75 years with LA-NSCLC were randomly assigned (1:1) to receive daily carboplatin (30 mg/m2) or weekly carboplatin (area under the curve, 2 mg·min/mL) plus nab-paclitaxel (30 mg/m2) with thoracic radiotherapy. Durvalumab maintenance therapy was recommended after treatment completion. The primary endpoint was overall survival, which was used to assess the non-inferiority of weekly carboplatin plus nab-paclitaxel compared to daily low-dose carboplatin. RESULTS: From December 2020 to March 2024, 124 patients were enrolled (carboplatin arm, 61 and carboplatin plus nab-paclitaxel arm, 63). In the planned interim analysis, the Bayesian predictive probability indicating the non-inferiority of carboplatin plus nab-paclitaxel compared with carboplatin in the final analysis was 8.0%, leading to early study termination for futility. The median overall survival was not estimable in the carboplatin arm; the estimated value in the carboplatin plus nab-paclitaxel arm was 26.1 months (hazard ratio, 1.56; 95% confidence interval, 0.79-3.11; p = 0.200). Two treatment-related and seven non-cancer-related deaths occurred in the carboplatin plus nab-paclitaxel arm. Patients in the carboplatin arm had better quality of life than those in the carboplatin plus nab-paclitaxel arm at 6 weeks (odds ratio, 0.39; 95% confidence interval, 0.18-0.81; p = 0.012). CONCLUSIONS: Daily low-dose carboplatin with concurrent thoracic radiotherapy remains the standard treatment for older patients with unresectable LA-NSCLC in Japan.

Humans↗

PubMed2005

Immunogenicity and safety of BERNA-YF compared with two other 17D yellow fever vaccines in a phase 3 clinical trial.

BERNA-YF (Flavimun) is a live, attenuated yellow fever (YF) vaccine of the 17D strain produced by Berna Biotech Ltd. following a transfer of technology from the Robert Koch Institute (RKI) in Berlin, Germany. In this phase 3 bridging study, the immunogenicity and safety of BERNA-YF were compared with the original RKI YF vaccine (RKI-YF) and to a current, commercially available YF vaccine, Stamaril (AP-YF; Aventis Pasteur, Lyon, France), in 304 healthy, adult volunteers. All three vaccines elicited an effective immune response with seroprotection achieved in 100% of individuals in each vaccine group at a neutralizing antibody titer > or = 1:10. BERNA-YF was shown to be comparable to the other two vaccine products, and subgroup analysis showed no differences in immune response between three consecutive production batches. The immune response to BERNA-YF and RKI-YF was very similar, with no significant difference in antibody titer between the two groups (P = 0.4634). However, AP-YF vaccination resulted in a significantly lower antibody titer (P < 0.0001 versus BERNA-YF). Males exhibited a higher antibody response than females to both BERNA-YF and RKI-YF, but not to AP-YF. All three vaccines were well tolerated and no serious adverse events were reported.

Adult↗

PubMed2006

Diagnostic PCR analysis of the occurrence of methicillin and tetracycline resistance genes among Staphylococcus aureus isolates from phase 3 clinical trials of tigecycline for complicated skin and skin structure infections.

Diagnostic PCR assays were developed to track common genetic determinants of oxacillin resistance as well as resistance to classical tetracyclines in Staphylococcus aureus isolates from the recently completed worldwide phase 3 clinical trials of tigecycline. A total of 503 unique S. aureus strains isolated from complicated skin and skin structure infections were analyzed. The mecA gene was amplified from 120 strains (23.9%) determined to be resistant to oxacillin (MICs > or = 4 microg/ml). The prevalence of the mecA gene was found to vary regionally from 6.5% to 50.9% among isolates originating in Eastern Europe and North America, respectively. The presence of a tetracycline resistance determinant, tet(M) or tet(K), among methicillin-resistant S. aureus (MRSA) isolates also varied regionally, with a range of 11.9% to 46.2% among isolates tested from North America and Eastern Europe, respectively. The occurrence of a tetracycline resistance marker in methicillin-susceptible S. aureus (MSSA) strains varied from 2.5 to 16.1% among the isolates tested across the regions of study. The presence of tet(M) or tet(K) had no discernible effect on the tigecycline MICs for either MRSA or MSSA strains, which is consistent with the ability of the glycylcyclines to retain activity in the presence of both the ribosomal protection and efflux mechanisms of resistance to the tetracyclines.

Clinical Trials, Phase II as Topic↗

PubMed2005

A phase 3 study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with beta-thalassemia.

Deferasirox (ICL670) is a once-daily oral iron chelator developed for the treatment of chronic iron overload from blood transfusions. A comparative phase 3 trial was conducted to demonstrate the efficacy of deferasirox in regularly transfused patients with beta-thalassemia aged 2 years or older. Patients were randomized and received treatment with deferasirox (n = 296) or deferoxamine (n = 290), with dosing of each according to baseline liver iron concentration (LIC). The primary endpoint was maintenance or reduction of LIC; secondary endpoints included safety and tolerability, change in serum ferritin level, and net body iron balance. In both arms, patients with LIC values of 7 mg Fe/g dry weight (dw) or higher had significant and similar dose-dependent reductions in LIC and serum ferritin, and effects on net body iron balance. However, the primary endpoint was not met in the overall population, possibly due to the fact that proportionally lower doses of deferasirox relative to deferoxamine were administered to patients with LIC values less than 7 mg Fe/g dw. The most common adverse events included rash, gastrointestinal disturbances, and mild nonprogressive increases in serum creatinine. No agranulocytosis, arthropathy, or growth failure was associated with deferasirox administration. Deferasirox is a promising once-daily oral therapy for the treatment of transfusional iron overload.

Administration, Oral↗

PubMed2005

[Geographic variation in the prevalence of asthma symptoms in Spanish children and adolescents. International Study of Asthma and Allergies in Childhood (ISAAC) Phase 3, Spain].

OBJECTIVE: To analyze geographic variations in the prevalence of symptoms related to asthma in Spanish children and adolescents. POPULATION AND METHODS: In 2001 and 2002, the Spanish arm of the International Study of Asthma and Allergies in Childhood (ISAAC) Phase 3 collected information on 28 445 children in the age bracket of 6-7 years in 10 metropolitan areas (A Coruña, Asturias, Barcelona, Bilbao, Cartagena, Castellón, Madrid, Pamplona, San Sebastián, and Valencia) and on 31 257 adolescents in the bracket 13-14 years in 11 areas (the previously named areas plus Valladolid). An asthma symptom questionnaire was filled in by parents or the adolescents themselves. Differences in symptoms between geographic areas were analyzed by fitting a logistic regression model. The relationship between symptoms and age was analyzed by linear correlation. RESULTS: The prevalence of recent wheezing (last 12 months) ranged from 7.1% to 12.9% among 6-7-year-olds and from 7.1% to 15.3% among the 13-14-year-olds. The greatest risk of recent wheezing was observed for children in A Coruña (odds ratio [OR] =1.96 in comparison with the area of lowest prevalence; 95% confidence interval [CI], 1.65-2.33) and Bilbao (OR=1.83; 95% CI, 1.54-2.18) and for adolescents in A Coruña (OR=2.38; 95% CI, 2.04-2.79) and Asturias (OR=2.37; 95% CI, 2.03-2.77). A strong correlation (r=0.72) was observed between the prevalence of recent wheezing and age in each of the geographic areas. CONCLUSIONS: Considerable geographic variation in the prevalence of asthma symptoms can be seen in Spain even among young children. Symptoms are more frequent in children and adolescents who live on the Spain s northern Atlantic coast.

Adolescent↗

PubMed2026

Safety and Tolerability of Oral Islatravir Once Monthly as Pre-exposure Prophylaxis in Cisgender Men and Transgender Women Who Have an Elevated Likelihood of HIV-1 Exposure: Results From the IMPOWER-24 Randomized Phase 3 Study.

BACKGROUND: Islatravir once monthly (qm), a nucleoside reverse transcriptase translocation inhibitor with a long half-life, was evaluated for safety and tolerability in cisgender men and transgender women who have sex with men and are at increased likelihood of HIV-1 (HIV) exposure. METHODS: IMPOWER-24 (NCT04652700) was a double-blind, Phase 3 study. Participants were randomized 2:1 to islatravir 60 mg oral qm or emtricitabine (FTC; 200 mg) coformulated with either tenofovir disoproxil (245 mg) or tenofovir alafenamide (TAF; 25 mg) once daily (qd). After ∼9 months, blinded islatravir was discontinued due to lymphocyte reductions; participants were offered open-label comparator for 20 months. RESULTS: In total, 494 participants were enrolled (328 islatravir; 166 comparator): 91.5% were cisgender men, 41.7% were White, and median age was 27 years. Mean blinded dosing duration was 4.7 months (islatravir) versus 4.3 months (comparator). Overall, 211 participants (64.3%) in the islatravir group and 128 (77.1%) in the comparator group had ≥1 adverse event (AE). Most AEs were mild or moderate, with 1 AE leading to product discontinuation (islatravir; gastroesophageal reflux). Serious AEs occurred in <2%; none were related to study product. Change in total lymphocytes in the islatravir group at Month 3 was -7.4%; a trend toward recovery was observed after islatravir was stopped. Mean total lymphocytes remained within normal range. No HIV infections occurred in either group during the double-blind phase. CONCLUSIONS: Islatravir qm was generally well tolerated; decreases in total lymphocytes were observed with islatravir. Original primary efficacy objectives were not assessed due to early study stoppage.

Humans↗

PubMed2005

Intrinsic character of the (3 x 3) to (square root 3 x square root 3) phase transition in Pb/Si(111).

We have investigated the (3 x 3) to (square root 3 x square root 3) reversible phase transition in Pb/Si(111) by means of variable temperature scanning tunneling microscopy and density functional first-principles calculations. By tracking exactly the same regions of the surface with atomic resolution in a temperature range between 40 and 200 K, we have observed the phase transition in real time. The ability to prepare and track exceptionally large domains without defects has allowed us to detect the intrinsic character of the phase transition at temperatures around 86 K. This intrinsic character is in full agreement with our first-principles calculations. Moreover, our results show that the hypothesis that point defects play a fundamental role as the driving force, reported for similar systems, can be discarded for Pb/Si(111).

Journal Article↗

PubMedDate not supplied

[The behavior of 3-phase scintigraphy of hip joint prostheses].

With the results of about 600 hip joint prostheses examined by scintigraphy, it is evident that nuclear medicine is more than a supplementary examination, especially in the case of a non-cemented isoelastic prosthesis. The combination of 3-phase scintigraphy with leukocyte scintigraphy could solve the problems of infected and aseptic displaced prostheses in 90% of the cases. The conventional X-ray diagnostic being the only method to demonstrate bone morphology is still the primary examination.

Femur↗

PubMed2005

Efficacy and safety of tigecycline monotherapy compared with vancomycin plus aztreonam in patients with complicated skin and skin structure infections: Results from a phase 3, randomized, double-blind trial.

OBJECTIVES: To compare the effect of tigecycline monotherapy, a first-in-class, expanded broad spectrum glycylcycline, with the combination of vancomycin and aztreonam (V + A) in the treatment of complicated skin and skin structure infections (cSSSI). METHODS: A phase 3, double-blind study conducted in 8 countries enrolled adults with cSSSI who required intravenous (IV) antibiotic therapy for > or =5 days. Patients were randomly assigned (1:1) to receive either tigecycline or V + A for up to 14 days. Primary endpoint was the clinical cure rate at the test-of-cure visit. Secondary endpoints included microbiologic efficacy and in vitro susceptibility to tigecycline of bacteria that cause cSSSI. Safety was assessed by physical examination, laboratory analyses, and adverse event reporting. RESULTS: A total of 596 patients were screened for enrollment, 573 were analyzed for safety, 537 were included in the clinical modified intent-to-treat (c-mITT) population, 397 were clinically evaluable (CE), and 228 were microbiologically evaluable (ME). At test-of-cure, cure rates were similar between tigecycline and V + A groups in the CE population (82.9% versus 82.3%, respectively) and in the c-mITT population (75.5% versus 76.9%, respectively). Microbiologic eradication rates (subject level) at test-of-cure in the ME population were also similar between tigecycline and V + A. Frequency of adverse events was similar between groups, although patients receiving tigecycline had higher incidence of nausea, vomiting, dyspepsia, and anorexia, while increased ALT/SGPT, pruritus, and rash occurred significantly more often in V + A-treated patients. CONCLUSIONS: This study demonstrates that the efficacy of tigecycline monotherapy for the treatment of patients with cSSSI is statistically noninferior to the combination of V + A.

Anti-Bacterial Agents↗

PubMed2026

Efficacy, Safety, and Pharmacokinetics of Upadacitinib Among Patients in East Asia With Moderately to Severely Active Ulcerative Colitis: A Post Hoc Subanalysis of Randomized Phase 3 Studies.

BACKGROUND AND AIM: Upadacitinib, a selective Janus kinase 1 inhibitor, is approved to treat moderately to severely active ulcerative colitis (UC). This post hoc subanalysis evaluated the efficacy, safety, and pharmacokinetics of upadacitinib in patients in East Asia. METHODS: U-ACHIEVE (UC1; NCT02819635) and U-ACCOMPLISH (UC2; NCT03653026) were Phase 3, multicenter, randomized, double-blind, induction studies evaluating upadacitinib 45 mg or placebo daily in adults with moderately to severely active UC. Clinical responders to 8 weeks of upadacitinib induction were eligible to receive upadacitinib 15 mg, upadacitinib 30 mg, or placebo daily in the 52-week U-ACHIEVE maintenance study (UC3; NCT02819635). Efficacy outcomes, safety, and pharmacokinetics were evaluated among East Asian patients. RESULTS: A higher proportion of East Asian patients achieved clinical remission with upadacitinib than placebo at induction Week 8 (UC1: n = 127, 31.4% vs. 7.3%; UC2: n = 114, 31.2% vs. 2.7%) and maintenance Week 52 (UC3: n = 184, upadacitinib 15 mg, 52.4%; upadacitinib 30 mg, 53.8%; placebo, 10.7%). Rates of endoscopic outcomes were higher with upadacitinib than with placebo across studies. No new safety signals were identified. Herpes zoster occurrences were low (UC1 and UC2: upadacitinib 45 mg, two events [in one patient]; placebo, zero events; UC3: upadacitinib 15 mg, five events; upadacitinib 30 mg, eight events; placebo, zero events). Pharmacokinetics and trends in the relationship between upadacitinib exposure and efficacy were consistent in the East Asian and global populations. CONCLUSION: Upadacitinib was generally well tolerated and effective for treating moderately to severely active UC in patients in East Asia, with a favorable benefit-risk profile consistent with the global population. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02819635, NCT03653026.

Humans↗

PubMed2026

Deucravacitinib 5-Year Safety and Efficacy Results in Plaque Psoriasis: A Phase 3 Open-Label Extension of Randomized Clinical Trials.

BACKGROUND: Deucravacitinib, an oral, selective, tyrosine kinase 2 inhibitor, is approved for adults with moderate to severe plaque psoriasis who are candidates for systemic therapy and for adults with active psoriatic arthritis. OBJECTIVE: We evaluated deucravacitinib safety and efficacy over 5 years in the phase 3 POETYK PSO-1, PSO-2, and long-term extension (LTE) trials in patients with moderate to severe plaque psoriasis. METHODS: PSO-1 and PSO-2 (parent trials) randomized patients 1:2:1 to oral placebo, deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily. At 52 weeks, patients enrolled in the LTE trial received open-label deucravacitinib. Safety was reported as exposure-adjusted incidence rates (EAIRs) per 100 person-years (PY). Clinician- and patient-reported outcomes were analyzed using modified nonresponder imputation in patients receiving continuous deucravacitinib from day 1 (PSO-1/PSO-2) through 5 years. RESULTS: Overall, 1519 patients received one or more deucravacitinib dose; total exposure was 5046.7 PY through data cutoff (September 2, 2024). EAIRs/100 PY were comparable or decreased from the 1-year to 5-year cumulative period for adverse events (AEs) (229.23, 127.40, respectively), serious AEs (5.68, 5.06), discontinuation due to AEs (4.38, 2.09), deaths (0.20, 0.22), serious infections excluding coronavirus disease 2019 (COVID-19) (1.53, 0.94), malignancies (1.02, 0.92), major adverse cardiovascular events (0.30, 0.34), and venous thromboembolism (0.20, 0.06). Clinical outcomes were well-maintained in patients receiving continuous deucravacitinib (n = 513) from 1 through 5 years, including achievement of a ≥ 75% reduction from baseline in the Psoriasis Area and Severity Index (1 year, 72.1% [95% CI 68.2-76.1]; 5 years, 67.3% [62.0-72.6]) and a static Physician Global Assessment score of 0 (clear) or 1 (almost clear) (1 year, 57.5% [53.1-61.9]; 5 years, 52.6% [47.0-58.1]). Dermatology Life Quality Index 0 or 1 was well-maintained from 1 year (52.5% [48.0-57.1]) through 5 years (45.4% [40.0-50.8]). CONCLUSIONS: These findings demonstrate a consistent safety profile with no new safety signals and durable clinical response through 5 years of treatment with deucravacitinib. CLINICAL TRIAL REGISTRATION: NCT03624127, NCT03611751, NCT04036435.

Humans↗

PubMed2026

Clinical Trial: Phase 3 Trial of Resmetirom Versus Placebo in Metabolic Dysfunction-Associated Steatohepatitis-Reanalysis of Fibrosis Stage 2-3 Subset.

BACKGROUND: Resmetirom is an oral thyroid hormone receptor beta agonist clinically used to treat metabolic dysfunction-associated steatohepatitis (MASH) among adults with stage F2 or F3 fibrosis. AIMS: Because the pivotal, 52-week, randomized, controlled, phase 3 MAESTRO-NASH trial (once-daily oral resmetirom 80 or 100 mg or placebo) included patients with F1, F2, or F3 fibrosis, we conducted a post hoc analysis aimed at assessing treatment response in the subset of patients with stages F2 and F3 fibrosis, consistent with the approved label population. METHODS: Co-primary end points were MASH resolution (hepatocellular ballooning score 0, lobular inflammation score ≤ 1, and ≥ 2-point nonalcoholic fatty liver disease activity score [NAS] reduction from baseline) with no fibrosis worsening, and ≥ 1-stage fibrosis improvement with no NAS worsening at Week 52. RESULTS: Among 917 patients with F2 or F3 fibrosis, metabolic risk factor prevalence was high (hypertension, 78.0%; dyslipidemia, 71.1%; type 2 diabetes, 67.0%). MASH resolution was achieved by 25.7% in the 80-mg group, 29.9% in the 100-mg group, and 9.5% in the placebo group (p < 0.0001 for both comparisons with placebo). Respective percentages with fibrosis improvement were 26.5%, 28.9%, and 17.3% (p < 0.01 for both comparisons). From baseline to Week 24, low-density lipoprotein cholesterol decreased by 11.7% and 13.7% in the 80- and 100-mg resmetirom groups, respectively, and increased by 2.3% with placebo (p < 0.0001 for both comparisons). No new safety signals emerged. CONCLUSION: Results among patients with F2 and F3 fibrosis were consistent with the primary MAESTRO-NASH analysis population, demonstrating efficacy and safety of resmetirom after 52 weeks.

Humans↗

PubMed2026

Insulin, Semaglutide and Dapagliflozin in Adults With Type 1 Diabetes: Design and Methods of Triple Therapy for Type 1 Diabetes (TTT1)-An International Phase 3 Clinical Trial.

AIMS: Attaining target glycaemia can be a challenge in Type 1 Diabetes (T1D) due to insulin-induced weight gain. Adjunct therapy with modern glucose-lowering agents developed for type 2 diabetes (T2D) has great potential but may be insufficiently efficacious and carries risks of hypoglycaemia and ketosis. We designed the first Phase 3 clinical trial to assess the efficacy and safety of adding a Glucagon-Like Peptide 1 receptor agonist (GLP-1RA) and a Sodium-Glucose Co-transporter (SGLT2) Inhibitor to insulin therapy in overweight and obese adults with T1D and glycaemia above target (HbA1c 7.5%-11.0% inclusive) (NCT03899402). MATERIALS AND METHODS: In Period 1, participants are randomized 2:1 (open label) for 26 weeks to semaglutide and insulin (uptitrated to 1.0 mg weekly) or standard insulin therapy. In Period 2, those randomized to semaglutide and insulin in Period 1 are further randomized (double-blind) for 26 weeks to dapagliflozin (10 mg daily) or placebo, in addition to semaglutide. The primary objective is to compare change in HbA1c on 'triple therapy' (dapagliflozin, semaglutide and insulin) with 'dual therapy' (placebo, semaglutide and insulin). Secondary objectives include comparisons of triple therapy with standard insulin therapy and dual therapy (semaglutide and insulin) with standard insulin therapy. Safety outcomes include hypoglycaemia and ketosis. A sample size recalculation during the trial based on analysis of masked data revised the original recruitment target from 114 to 82 participants. CONCLUSION: The TTT1 trial will provide clinically useful information on combination adjunct therapy in the treatment of T1D.

Humans↗

PubMed1996

[A phase 3 clinical trial of 123I-iomazenil, a new central-type benzodiazepine receptor imaging agent (Part 2)--Report on clinical usefulness in diagnosis of degenerative neurological diseases and mental disorders].

Iomazenil (IMZ) is a partial inverse agonist of central-type benzodiazepine receptors (BZR) which binds specifically to BZR with high affinity. A multi-center Phase 3 clinical study was performed to evaluate the clinical usefulness of 123I-IMZ-SPECT in the diagnosis of brain disorders in 169 patients with degenerative neurological diseases and 37 patients with mental disorders such as neurotic, stress-related and somatoform disorders. In dementia, the decrease in activity in late images, obtained three hours after administration of 123I-IMZ, correlated negatively with the dementia score. In Parkinson's disease and spinocerebellar degeneration. 123I-IMZ showed a more profound decrease in uptake in late images than seen in the cerebral blood flow (CBF) images, and this decrease was in proportion to the duration and severity of the illness. In mental disorders, the ratio of the late to early image counts showed a negative correlation with Hamilton's anxiety scale in all regions in the brain cortices. In panic disorders, the ratio of the cerebral count to the cerebellar count in the late images correlated negatively with the severity of the attack in the frontal, temporal and parietal cortices. These results suggest that 123I-IMZ-SPECT enables us to evaluate the neuronal damage in degenerative diseases and the decrease in the BZR binding potential in mental disorders.

Adult↗

PubMed2001

Blood levels of immune cells predict survival in myeloma patients: results of an Eastern Cooperative Oncology Group phase 3 trial for newly diagnosed multiple myeloma patients.

Previously, it was reported that patients with multiple myeloma (MM) who have higher baseline levels of blood CD4(+) or CD19(+) cells have longer survival. This article extends the analysis of immune cell levels and survival in a large cohort (N = 504) of patients with MM entered on Eastern Cooperative Oncology Group (ECOG) phase 3 trial (9486). Newly diagnosed patients with MM received 2 cycles of vincristine, bischloroethylnitrosourea, melphalan, cytoxan, prednisone (VBMCP) and were treated on one of 3 randomized arms: VBMCP with either interferon or high-dose cyclophosphamide, or VBMCP alone. Blood immune cell levels were studied at trial entry (baseline), after 2 cycles of chemotherapy, after 2 years of therapy, and at relapse. Baseline CD3(+), CD4(+), CD8(+), CD19(+), and CD4(+) subset cell levels were all positively associated with survival (P =.0087 to P <.0001). A multivariate analysis incorporating CD4(+) and CD19(+) cell levels defined 3 separate groups of patients with MM to survival outcome. Higher CD19(+) blood levels were positively associated with MM-patient survival at entry to the study, at year 2, and at relapse (P <.0001 at all 3 timepoints). Patients with MM had evidence of immune cell reconstitution after 2 years of therapy, but the rate and extent of recovery was greater for CD8(+), which was greater than CD4(+), which was greater than CD19(+). This latter data affirms the positive relationship between the quantitative status of the blood immune system in MM and survival. In addition, the importance of the CD19(+) blood cells to survival is evident throughout the course of MM. Therapeutic efforts to maintain an intact immune system may be crucial in maximizing chemotherapeutic and/or immunotherapy efforts in this disease.

Actuarial Analysis↗

PubMed2000

Acute thromboscintigraphy with (99m)Tc-apcitide: results of the phase 3 multicenter clinical trial comparing 99mTc-apcitide scintigraphy with contrast venography for imaging acute DVT. Multicenter Trial Investigators.

UNLABELLED: (99m)Tc-apcitide (formerly known as (99m)Tc-P280) is a radiolabeled peptide that binds with high affinity and specificity to the glycoprotein IIb/IIIa receptors expressed on the activated platelets that are involved in acute thrombosis. The purpose of the phase 3 multicenter clinical trials was to compare (99m)Tc-apcitide scintigraphy with contrast venography for imaging acute deep venous thrombosis (DVT). METHODS: A total of 280 patients were enrolled in 2 clinical trials conducted in North America and Europe. Patients were to be within 10 d of onset of signs and symptoms of acute DVT or within 10 d of surgery associated with a high risk of DVT. (99m)Tc-apcitide scintigraphy and contrast venography were to be performed within 36 h. Planar scintigraphic images were obtained at 10, 60, and 120-180 min after injection. (99m)Tc-apcitide scintigrams and contrast venograms were read with masking and also by the institutional investigators. RESULTS: Of a total of 243 patients who were evaluable, 61.7% were receiving heparin at the time of imaging. Masked reading of (99m)Tc-apcitide scintigraphy, compared with masked reading of contrast venography, had a sensitivity, specificity, and agreement of 73.4%, 67.5%, and 69.1%, respectively, which met the prospectively defined target efficacy endpoint in both trials. Institutional reading of (99m)Tc-apcitide scintigraphy, compared with institutional reading of contrast venography, had a sensitivity, specificity, and agreement of 75.5%, 72.8%, and 74.0%, respectively. However, the entire trial population included patients with a history of DVT who may have had old, nonacute venous thrombi that could confound the venography results. Therefore, data from patients having no history of DVT or pulmonary embolism and who presented within 3 d of onset of signs and symptoms (n = 63), i.e., patients for whom a venogram would be expected to be positive only if acute DVT were present, also were analyzed as a subset. In these patients, institutional reading of (99m)Tc-apcitide scintigraphy, compared with institutional reading of contrast venography, had a sensitivity, specificity, and agreement of 90.6%, 83.9%, and 87.3%, respectively. CONCLUSION: (99m)Tc-apcitide scintigraphy is a new diagnostic modality that is highly sensitive for imaging acute DVT.

Acute Disease↗