A randomized, placebo-controlled trial of celecoxib in men prior to receiving prostatectomy for clinically localized adenocarcinoma of the prostate: Evaluation of drug-specific biomarker modulation

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5001-5001 ◽  
Author(s):  
M. A. Carducci ◽  
J. R. Walczak ◽  
E. Heath ◽  
W. G. Nelson ◽  
A. M. DeMarzo ◽  
...  
Keyword(s):  
Tumor Tissue ◽  
Controlled Trial ◽  
Clinical Stage ◽  
Double Blind Study ◽  
Mrna Levels ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Ki 67 ◽  
Tissue Samples ◽  
Cox 2

5001 Background: Cyclooxygenase-2 (COX-2) has been postulated as a pharmacological target for preventing a variety of epithelial malignancies including prostate cancer (PCa). We conducted a randomized, double-blind study evaluating celecoxib (C) on biomarkers in normal and PCa tissue at prostatectomy (RRP). Methods: Patients with Gleason sum ≥ 7, pre-study PSA ≥ 15 ng/ml, clinical stage T2b, T2c, or any combination of PSA, Stage, or two or more cores positive for PCa received either C at 400 mg po bid or placebo for 4–6 wks pre-RRP. The primary endpoint was to compare and correlate tissue PG levels with histologic and secondary endpoints performed on prostate tissue and serum from the two comparable groups. Outcomes included PG levels, quantitative RT-PCR for mRNA levels of COX-1 and COX-2, oxidized DNA bases; measurement of apoptosis, proliferation, angiogenic-potential assays and histologic comparison of treated/untreated tissue specimens; PSA levels; and tissue levels of C. Estimates of change in endpoints required 30 patients per arm. Results: Seventy three subjects consented with 64 randomized and included in the intent to treat analysis; 2 had missing data for primary endpoints. Age, baseline PSA, race and Gleason score were comparable across treatment groups. The regimen was well tolerated with no serious adverse events. There was no treatment effect observed in the PG, COX mRNA levels or oxidized DNA base levels in the RRP specimens. Tumor tissue contained significantly less COX-2 mRNA levels than benign tissue (p=<0.0001). Of the markers of apoptosis and proliferation assessed, Ki-67 was higher in tumor samples, and p21 was less in C treated samples. Celecoxib was present in tumor tissue demonstrating that it reached the target, but there were no observed effects in the study endpoints. There was no toxicity greater grade 1 except hepatic toxicity in a placebo group subject. Conclusions: Our results show a lack of effect of C on PCa despite demonstrating that C was present in tissue samples. At this time, we cannot recommend further studies of C as a PCa preventative agent when dosed at 400 mg PO BID. The study was supported by a grant from the NCI, DCP (#NO1-CN-95000–46) and Pfizer, Inc. No significant financial relationships to disclose.

scholarly journals Phase II, Randomized, Placebo-Controlled Trial of Neoadjuvant Celecoxib in Men With Clinically Localized Prostate Cancer: Evaluation of Drug-Specific Biomarkers

2009 ◽  
Vol 27 (30) ◽  
pp. 4986-4993 ◽  
Author(s):  
Emmanuel S. Antonarakis ◽  
Elisabeth I. Heath ◽  
Janet R. Walczak ◽  
William G. Nelson ◽  
Helen Fedor ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Controlled Trial ◽  
Clinical Stage ◽  
Specific Antigen ◽  
Prostate Tissue ◽  
Localized Prostate Cancer ◽  
Double Blind ◽  
Ki 67 ◽  
End Points ◽  
Cox 2

Purpose Cyclooxygenase-2 (COX-2) is a potential pharmacologic target for the prevention of various malignancies, including prostate cancer. We conducted a randomized, double-blind trial to examine the effect of celecoxib on drug-specific biomarkers from prostate tissue obtained at prostatectomy. Patients and Methods Patients with localized prostate cancer and Gleason sum ≥ 7, prostate-specific antigen (PSA) ≥ 15 ng/mL, clinical stage T2b or greater, or any combination with greater than 45% risk of capsular penetration were randomly assigned to celecoxib 400 mg by mouth twice daily or placebo for 4 to 6 weeks before prostatectomy. The primary end point was the difference in prostatic prostaglandin levels between the two groups. Secondary end points were differences in COX-1 and -2 expressions; oxidized DNA bases; and markers of proliferation, apoptosis and angiogenesis. Tissue celecoxib concentrations also were measured. Tertiary end points were drug safety and compliance. Results Seventy-three patients consented, and 64 were randomly assigned and included in the intention-to-treat analysis. There were no treatment differences in any of the primary or secondary outcomes. Multivariable regression revealed that tumor tissue had significantly lower COX-2 expression than benign prostatic tissue (P = .01) and significantly higher levels of the proliferation marker Ki-67 (P < .0001). Celecoxib was measurable in prostate tissue of patients on treatment, demonstrating that celecoxib reached its target. Celecoxib was safe and resulted in only grade 1 toxicities. Conclusion Treatment with 4 to 6 weeks of celecoxib had no effect on intermediate biomarkers of prostate carcinogenesis, despite the achievement of measurable tissue levels. We caution against using celecoxib 400 mg twice daily as a preventive agent for prostate cancer in additional studies.

IDH1 mutation detection in plasma circulating tumor DNA (ctDNA) and association with clinical response in patients with advanced intrahepatic cholangiocarcinoma (IHC) from the phase III ClarIDHy study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4576-4576 ◽  
Author(s):  
Elia Aguado ◽  
Ghassan K. Abou-Alfa ◽  
Andrew X. Zhu ◽  
Teresa Macarulla ◽  
Bin Fan ◽  
...  
Keyword(s):  
Clinical Response ◽  
Tumor Tissue ◽  
Digital Pcr ◽  
Idh1 Mutation ◽  
Phase Iii ◽  
Selection Strategy ◽  
Double Blind Study ◽  
Isocitrate Dehydrogenase 1 ◽  
Double Blind ◽  
Tissue Samples

4576 Background: Mutations in isocitrate dehydrogenase 1 ( IDH1) are detected in ~13% of IHCs. Ivosidenib (IVO) is a first-in-class, oral inhibitor of the mutant IDH1 (mIDH1) protein. In ClarIDHy, a global, phase 3, double-blind study in previously treated patients with advanced m IDH1 IHC (N = 186), IVO demonstrated an improvement in progression-free survival (PFS) vs placebo (hazard ratio 0.37, p < 0.001) (Abou-Alfa et al., Ann Oncol 2019; NCT02989857). Feasibility of m IDH1 detection in plasma ctDNA from patients with IHC was demonstrated and was highly concordant with mutation status in tumor tissue (Aguado-Fraile et al., Cancer Res 2019). This analysis was extended to the larger patient cohort from ClarIDHy, and longitudinal m IDH1 detection from ctDNA was assessed and correlated with clinical response. Methods: Baseline plasma and tumor tissue samples were obtained before randomization; longitudinal plasma samples were collected on day 1 of each treatment cycle. m IDH1 status in tissue was prospectively and centrally confirmed using Oncomine Focus Assay. A BEAMing digital PCR test was used for quantification of m IDH1 in plasma. IDH1 mutation clearance ( IDH1-MC) was achieved when plasma m IDH1 variant allele frequency was below the assay’s sensitivity (0.02% for R132C/L/S/G; 0.04% for R132H). Results: m IDH1 detection in plasma ctDNA and tissue was concordant in 92% (193/210) of samples screened. As of 31 Jan 2019, median PFS was 2.7 months for IVO vs 1.4 months for placebo. Longitudinal analysis with biomarker data available as of Jan 2020 demonstrated IDH1-MC in plasma from 10 IVO-treated patients with PFS ≥2.7 months (n = 36) vs 0 patients with PFS < 2.7 months (n = 40). No IDH1-MC was observed in patients treated with placebo, irrespective of response (n = 49). Conclusions: These results reinforce the feasibility of IDH1-R132 detection in plasma from patients with IHC, with a 92% concordance with detection in tumor tissue, supporting m IDH1 detection in liquid biopsy as a viable patient selection strategy where tissue exhaustion can limit conventional methods. Plasma IDH1-MC was also observed in a subset of IVO-treated patients who achieved disease control. Clinical trial information: NCT02989857 .

scholarly journals Safety and efficacy of intravenous belimumab in children with systemic lupus erythematosus: results from a randomised, placebo-controlled trial

2020 ◽  
Vol 79 (10) ◽  
pp. 1340-1348 ◽  
Author(s):  
Hermine I Brunner ◽  
Carlos Abud-Mendoza ◽  
Diego O Viola ◽  
Inmaculada Calvo Penades ◽  
Deborah Levy ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Controlled Trial ◽  
Geometric Mean ◽  
Well Being ◽  
Statistical Testing ◽  
Double Blind Study ◽  
Systemic Lupus ◽  
Serious Adverse Events ◽  
Double Blind

ObjectivesThis ongoing Phase-2, randomised, placebo-controlled, double-blind study evaluated the efficacy, safety and pharmacokinetics of intravenous belimumab in childhood-onset systemic lupus erythematosus (cSLE).MethodsPatients (5 to 17 years) were randomised to belimumab 10 mg/kg intravenous or placebo every 4 weeks, plus standard SLE therapy. Primary endpoint: SLE Responder Index (SRI4) response rate (Week 52). Key major secondary endpoints: proportion of patients achieving the Paediatric Rheumatology International Trials Organisation/American College of Rheumatology (PRINTO/ACR) response using 50 and ‘30 alternative’ definitions (Week 52), and sustained response (Weeks 44 to 52) by SRI4 and Parent Global Assessment of well-being (Parent-global). Safety and pharmacokinetics were assessed. Study not powered for statistical testing.ResultsNinety-three patients were randomised (belimumab, n=53; placebo, n=40). At Week 52, there were numerically more SRI4 responders with belimumab versus placebo (52.8% vs 43.6%; OR 1.49 (95% CI 0.64 to 3.46)). PRINTO/ACR 30 alternative (52.8% vs 27.5%; OR 2.92 (95% CI 1.19 to 7.17)) and PRINTO/ACR 50 (60.4% vs 35.0%; OR 2.74 (95% CI 1.15 to 6.54)) responses were more frequent with belimumab than placebo, as were sustained responses for SRI4 (belimumab, 43.4%; placebo, 41.0%; OR 1.08 (95% CI 0.46 to 2.52)) and Parent-global (belimumab, 59.1%; placebo, 33.3%; OR 3.49 (95% CI 1.23 to 9.91)). Serious adverse events were reported in 17.0% of belimumab patients and 35.0% of placebo patients; one death occurred (placebo). Week-52, geometric mean (95% CI) belimumab trough concentration was 56.2 (45.2 to 69.8) µg/mL.ConclusionThe belimumab intravenous pharmacokinetics and benefit–risk profile in cSLE are consistent with adult belimumab studies and the 10 mg/kg every 4 weeks dose is appropriate.Trial registration numberNCT01649765.

scholarly journals Long-Term Safety and Efficacy of Prebiotic Enriched Infant Formula—A Randomized Controlled Trial

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1276
Author(s):  
Franka Neumer ◽  
Orenci Urraca ◽  
Joaquin Alonso ◽  
Jesús Palencia ◽  
Vicente Varea ◽  
...  
Keyword(s):  
Infant Formula ◽  
Controlled Trial ◽  
Fecal Microbiota ◽  
First Year ◽  
Double Blind Study ◽  
Double Blind ◽  
Term Infants ◽  
Intention To Treat ◽  
Prebiotic Oligosaccharides ◽  
First Year Of Life

The present study aims to evaluate the effects of an infant formula supplemented with a mixture of prebiotic short and long chain inulin-type oligosaccharides on health outcomes, safety and tolerance, as well as on fecal microbiota composition during the first year of life. In a prospective, multicenter, randomized, double-blind study, n = 160 healthy term infants under 4 months of age were randomized to receive either an infant formula enriched with 0.8 g/dL of Orafti®Synergy1 or an unsupplemented control formula until the age of 12 months. Growth, fever (>38 °C) and infections were regularly followed up by a pediatrician. Digestive symptoms, stool consistency as well as crying and sleeping patterns were recorded during one week each study month. Fecal microbiota and immunological biomarkers were determined from a subgroup of infants after 2, 6 and 12 months of life. The intention to treat (ITT) population consisted of n = 149 infants. Both formulae were well tolerated. Mean duration of infections was significantly lower in the prebiotic fed infants (p < 0.05). The prebiotic group showed higher Bifidobacterium counts at month 6 (p = 0.006), and higher proportions of Bifidobacterium in relation to total bacteria at month 2 and 6 (p = 0.042 and p = 0.013, respectively). Stools of infants receiving the prebiotic formula were softer (p < 0.05). Orafti®Synergy1 tended to beneficially impact total daily amount of crying (p = 0.0594). Supplementation with inulin-type prebiotic oligosaccharides during the first year of life beneficially modulates the infant gut microbiota towards higher Bifidobacterium levels at the first 6 months of life, and is associated with reduced duration of infections.

scholarly journals Efficacy and safety of butylphthalide for patients who had acute ischaemic stroke receiving intravenous thrombolysis or endovascular treatment (BAST trial): study protocol for a randomised placebo-controlled trial

BMJ Open ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. e045559
Author(s):  
Xuelei Zhang ◽  
Anxin Wang ◽  
Jing Yu Zhang ◽  
Baixue Jia ◽  
Xiaochuan Huo ◽  
...  
Keyword(s):  
Ischaemic Stroke ◽  
Endovascular Treatment ◽  
Functional Outcome ◽  
Acute Ischaemic Stroke ◽  
Controlled Trial ◽  
Intravenous Thrombolysis ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Ischaemic Injury ◽  
Study Results

IntroductionAs a neuroprotective medication, butylphthalide (NBP) may help protect against cerebral ischaemic injury. However, evidence on whether NBP influences the outcomes of patients who had acute ischaemic stroke who are receiving revascularisation treatment is limited. This study aims to evaluate whether additional NBP therapy can improve the functional outcome of patients who receive intravenous recombinant tissue plasminogen activator and/or endovascular treatment (EVT).Methods and analysisThe study will be a randomised, double-blind, placebo-controlled, multiple-centre, parallel group trial. The sample size is estimated at 1200 patients. Eligible patients will be randomised at a 1:1 ratio to receive either NBP or placebo daily for 90 days, which will include 14 days of injections and 76 days of capsules. The first use of NBP/placebo will be started within 6 hours of onset of ischaemic stroke. The primary outcome is the functional outcome as assessed by the 90-day modified Rankin Scale, adjusted for baseline scores on the National Institutes of Health Stroke Scale. The primary safety outcome is the percentage of serious adverse events during the 90 days of treatment. This trial will determine whether NBP medication benefits patients who had acute ischaemic stroke who receive intravenous thrombolysis or EVT.Ethics and disseminationThe protocol was written according to the general ethical guidelines of the Declaration of Helsinki and approved by the Institutional Review Board/Ethics Committee of Beijing Tiantan Hospital, Capital Medical University with approval number KY 2018-003-02. Ethics committees of all participating sites have approved the study . Results of the study will be published in peer-reviewed scientific journals and shared in scientific presentations.Trial registration numberNCT03539445.

scholarly journals Olokizumab, a monoclonal antibody against interleukin 6, in combination with methotrexate in patients with rheumatoid arthritis inadequately controlled by methotrexate: efficacy and safety results of a randomised controlled phase III study

2021 ◽  
pp. annrheumdis-2021-219876
Author(s):  
Evgeniy Nasonov ◽  
Saeed Fatenejad ◽  
Eugen Feist ◽  
Mariana Ivanova ◽  
Elena Korneva ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Activity Index ◽  
Disease Activity Index ◽  
Phase Iii ◽  
Double Blind Study ◽  
Efficacy And Safety ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Acr20 Response

ObjectiveTo evaluate the efficacy and safety of olokizumab (OKZ) in patients with active rheumatoid arthritis despite treatment with methotrexate (MTX).MethodsIn this 24-week multicentre, placebo-controlled, double-blind study, patients were randomised 1:1:1 to receive subcutaneously administered OKZ 64 mg once every 2 weeks, OKZ 64 mg once every 4 weeks, or placebo plus MTX. The primary efficacy endpoint was the proportion of patients achieving an American College of Rheumatology 20% (ACR20) response at week 12. The secondary efficacy endpoints included percentage of subjects achieving Disease Activity Score 28-joint count based on C reactive protein <3.2, Health Assessment Questionnaire Disability Index at week 12, ACR50 response and Clinical Disease Activity Index ≤2.8 at week 24. Safety and immunogenicity were assessed throughout the study.ResultsA total of 428 patients were randomised. ACR20 responses were more frequent with OKZ every 2 weeks (63.6%) and OKZ every 4 weeks (70.4%) than placebo (25.9%) (p<0.0001 for both comparisons). There were significant differences in all secondary efficacy endpoints between OKZ-treated arms and placebo. Treatment-emergent serious adverse events (TESAEs) were reported by more patients in the OKZ groups compared with placebo. Infections were the most common TESAEs. No subjects developed neutralising antidrug antibodies.ConclusionsTreatment with OKZ was associated with significant improvement in signs, symptoms and physical function of rheumatoid arthritis without discernible differences between the two regimens. Safety was as expected for this class of agents. Low immunogenicity was observed.Trial registration numberNCT02760368.

scholarly journals Safety, pharmacokinetics and antiviral activity of PGT121, a broadly neutralizing monoclonal antibody against HIV-1: a randomized, placebo-controlled, phase 1 clinical trial

2021 ◽  
Author(s):  
Kathryn E. Stephenson ◽  
Boris Julg ◽  
C. Sabrina Tan ◽  
Rebecca Zash ◽  
Stephen R. Walsh ◽  
...  
Keyword(s):  
Viral Load ◽  
T Cell ◽  
Adverse Events ◽  
Antiviral Activity ◽  
Controlled Trial ◽  
Phase 1 ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Cell Counts ◽  
Hiv 1

AbstractHuman immunodeficiency virus (HIV)-1-specific broadly neutralizing monoclonal antibodies are currently under development to treat and prevent HIV-1 infection. We performed a single-center, randomized, double-blind, dose-escalation, placebo-controlled trial of a single administration of the HIV-1 V3-glycan-specific antibody PGT121 at 3, 10 and 30 mg kg–1 in HIV-uninfected adults and HIV-infected adults on antiretroviral therapy (ART), as well as a multicenter, open-label trial of one infusion of PGT121 at 30 mg kg–1 in viremic HIV-infected adults not on ART (no. NCT02960581). The primary endpoints were safety and tolerability, pharmacokinetics (PK) and antiviral activity in viremic HIV-infected adults not on ART. The secondary endpoints were changes in anti-PGT121 antibody titers and CD4+ T-cell count, and development of HIV-1 sequence variations associated with PGT121 resistance. Among 48 participants enrolled, no treatment-related serious adverse events, potential immune-mediated diseases or Grade 3 or higher adverse events were reported. The most common reactions among PGT121 recipients were intravenous/injection site tenderness, pain and headache. Absolute and relative CD4+ T-cell counts did not change following PGT121 infusion in HIV-infected participants. Neutralizing anti-drug antibodies were not elicited. PGT121 reduced plasma HIV RNA levels by a median of 1.77 log in viremic participants, with a viral load nadir at a median of 8.5 days. Two individuals with low baseline viral loads experienced ART-free viral suppression for ≥168 days following antibody infusion, and rebound viruses in these individuals demonstrated full or partial PGT121 sensitivity. The trial met the prespecified endpoints. These data suggest that further investigation of the potential of antibody-based therapeutic strategies for long-term suppression of HIV is warranted, including in individuals off ART and with low viral load.

scholarly journals Corrigendum: Nutritional Evaluation and Optimisation in Neonates (NEON) trial of amino acid regimen and intravenous lipid composition in preterm parenteral nutrition: a randomised double-blind controlled trial

2017 ◽  
Vol 3 (2) ◽  
pp. 81-82
Author(s):  
Sabita Uthaya ◽  
Xinxue Liu ◽  
Daphne Babalis ◽  
Caroline Dore ◽  
Jane Warwick ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Analysis Data ◽  
Secondary Outcome ◽  
Final Report ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Correct Treatment ◽  
Data Set ◽  
Study Results ◽  
Made In

Abstract During the uploading of data for submission to the EudraCT results database, a discrepancy was identified. It was noted that the number of deaths per group was not consistent with the number in the final report and trial publication. This discrepancy was found to relate to two randomisation numbers. During the trial, the randomisation database had been held separately from the trial database, with manual transcription of randomisation numbers from the randomisation database to the trial database. Two randomisation numbers had been entered incorrectly into the trial database and, although this was documented at the time, the correction had not been made in the analysis data set. The two infants in question received the correct treatment in accordance with their allocation, but were analysed according to the wrong treatment group. Following the identification of this error, all analyses were repeated. It was confirmed that this error had a negligible impact on the study results. Furthermore, the two infants in question had not been included in the primary and secondary outcome analyses, as one had died and the other had withdrawn prior to the primary end-point assessment, so the key study outcomes remain unchanged. The only changes to the results are in the number of serious adverse events and minor changes to the data in demographics tables mostly affecting decimal points and the CONSORT diagram. Our interpretation of the study results remains unchanged.

A Controlled Trial of Extended-Release Guanfacine and Psychostimulants on Executive Function and ADHD

2018 ◽  
Vol 24 (2) ◽  
pp. 318-325 ◽  
Author(s):  
Judy P. M. van Stralen
Keyword(s):  
Executive Function ◽  
Adverse Events ◽  
Extended Release ◽  
Rating Scale ◽  
Controlled Trial ◽  
Severity Of Illness ◽  
P Value ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Stimulant Therapy

Objective: To evaluate the effectiveness of guanfacine extended-release (GXR) versus placebo as adjunct therapy to usual care stimulant therapy in improving executive function in children aged 6 to 12 years diagnosed with ADHD. Method: In this single center, double-blind placebo-controlled crossover trial, subjects continued to take their psychostimulant and were randomly assigned at baseline to receive active treatment or placebo first. Efficacy measures included Behavioural Rating Inventory of Executive Function (BRIEF-P), ADHD Rating Scale IV (ADHD-RS IV), and Clinical Global Impressions of Severity of Illness (CGI-S) and Improvement (CGI-I) scales. Safety measures included adverse events and vital signs. Results: Significant benefits of GXR plus psychostimulant were observed on BRIEF-P ( p value = .0392), ADHD-RS-IV ( p < .0001), CGI-S ( p = .0007), and CGI-I ( p = .003). There were no serious adverse events and no new safety signals. Conclusion: Use of GXR as adjunctive therapy to stimulant therapy significantly improves executive function in children with ADHD.

scholarly journals Daily Oral Administration of the Novel Androgen 11β-MNTDC Markedly Suppresses Serum Gonadotropins in Healthy Men

2020 ◽  
Vol 105 (3) ◽  
pp. e835-e847 ◽  
Author(s):  
Fiona Yuen ◽  
Arthi Thirumalai ◽  
Cindy Pham ◽  
Ronald S Swerdloff ◽  
Bradley D Anawalt ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Double Blind Study ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Healthy Men ◽  
Drug Concentrations ◽  
Serum Gonadotropin

Abstract Background 11β-methyl-19-nortestosterone (11β-MNT) is a modified testosterone (T) with androgenic and progestational activity. A single oral dose of the prodrug, 11β-MNT dodecylcarbonate (11β-MNTDC), was well tolerated in healthy men. Methods We conducted a randomized, double-blind study at 2 academic medical centers. 42 healthy men (18–50 years) were randomized to receive oral placebo or 11β-MNTDC, 200 or 400 mg daily, for 28 consecutive days. Primary outcome (safety and tolerability) measures were assessed twice per week. Subjects underwent serial blood sampling over 24 hours on days 1 and 28 to assess secondary outcomes: pharmacokinetics (serum drug concentrations); pharmacodynamics of 11β-MNTDC (serum sex steroids and gonadotropins); and mood and sexual function (via validated questionnaires). Results There were no serious adverse events. No participants discontinued because of an adverse event or laboratory test abnormality. 11β-MNTDC resulted in a dose-related increase in serum 11β-MNTDC and 11β-MNT concentrations sustained over 24 hours. Administration of 11β-MNTDC resulted in a marked suppression of serum gonadotropins, T, calculated free T, estradiol, and SHBG over the treatment period (P &lt; 0.01). Adverse effects that may be related to 11β-MNTDC included weight gain, acne, headaches, fatigue, and mild mood changes, with 5 men reporting decreased libido and 3 decreased erectile/ejaculatory function. Serum low-density lipoprotein cholesterol, weight (~2 kg), hematocrit, and hemoglobin increased and serum high-density lipoprotein cholesterol decreased in both 11β-MNTDC groups. Conclusion Daily oral 11β-MNTDC for 28 days in healthy men markedly suppressed serum gonadotropin and T concentrations without serious adverse effects. These results warrant further evaluation of 11β-MNTDC as a potential male oral contraceptive.

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