This amendment was implemented at the request of the sponsor and aimed to introduce the following changes in the conduct of the trial: - An analysis of prostaglandins in urine samples collected at Visits 1 and 3 from patients at selected centers in Poland in Germany was added. - Number and volume of urine samples were corrected due to the newly introduced analysis of prostaglandins in these samples. - Inclusion criterion No. 3 was further specified for clarity as follows: Sum-score of the three main uUTI symptoms (dysuria [“feeling pain or burning when passing urine”, No. 3], pollakisuria [“frequent urination of small volumes of urine”, No. 1], and urgency [“Urgent urination”, No. 2]) reported on the ACSS-Typical domain at Visit 1 is ≥ 6. - Inclusion criterion No. 3 was further specified as follows: Patients who took anti-inflammatory or analgesic drugs (eg, ibuprofen, paracetamol, acetylsalicylic acid) or spasmolytics for any reason within 24 hours prior to Visit 1, and/or are not willing to stop the intake of any of the following medication not permitted for use during the trial: Rosmarini folium, Levistici radix, and Centaurii herba supplements other than the CLR (IMP), antiinflammatory or analgesic drugs (eg, ibuprofen, acetylsalicylic acid, with exception of paracetamol), spasmolytics, herbal drugs or supplements, cranberry juice, and kidney or bladder teas. - The analgesic drugs added to exclusion criterion 10 were included in the list of prohibited concomitant medications.

The main objective of this amendment was to introduce changes in CTP Version 4, 11-MAR-2016, following from the sponsor’s decision to cancel the planned interim analysis. The decision for withdrawal of the interim analysis was justified with the markedly increased recruitment rates over the last 4 months of the trial conduct (up to 2 patients per trial site per month) and the expectation of a further increasing recruitment rate due to additionally initiated sites (see below). Other relevant changes implemented in CTP Version 5 with Amendment No. 2 included: - Prolongation of recruitment period by 4 months and of overall trial duration by 6 months accordingly. - Romania was excluded from the list of participating countries, because the conduct of- the trial in this country was disapproved by the local competent authority; consequently, the sponsor decided to increase the number of trial sites in Germany, Ukraine and Poland. - The list of concomitant medications not permitted during the trial was further specified by including an exception rule for spasmolytics, anti-inflammatory or analgesic drugs, and any additional AB therapy for other than acute lower uUTI indications. - The range of kit-No was updated since new IMP had been produced (the IMP for Ukraine had expired and not enough IMP was available for all countries). - Benefit-risk information with regard to the use of fosfomycin in the trial was updated in accordance with the latest version of the Summary of Product Characteristics of fosfomycin.